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Molecules to Medicine > Unit 3 > Flashcards

Unit 3 Flashcards

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Organic Chemistry 101 flashcards
1
Q

Five properties of malignant cells

A

1) Unresponsive to normal signals for proliferation control
2) De-differentiated (lack specialized function of neighboring tissues)
3) Invasive (capable of outgrowth into neighboring tissues)
4) Metastatic (capable of shedding cells that can drift through circulatory system and proliferate at other sites
5) Clonal in origin (derived from a single cell)

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2
Q

Benign tumors

A
  • Not metastatic and not invasive

- HAVE lost growth control and specialized function

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3
Q

Four steps of carcinogenesis

A

Tumor initiation, promotion,

conversion and progression are four of these steps.

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4
Q

Burkitt Lymphoma

A

dysregulation of c-myc gene by one of three chromosomal translocations

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5
Q

Autosomal dominant inherited cancer susceptibility

A

Familial Adenomatous Polyposis (FAP-APC gene), Familial Retinoblastoma (RB gene), familial Breast and Ovarian Cancer (BRCA1 and BRCA2 genes) and Wilms tumor syndromes.

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6
Q

Autosomal recessive inherited cancer susceptibility

A

cancers that are inherited as autosomal recessive disorders are Xeroderma pigmentosa (XP
genes), Ataxia-telangiectasia (AT gene), Bloom’s syndrome and Fanconi’s congenital aplastic
anemia (FA genes).

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7
Q

Retinoblastoma protein locus

A

13q14

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8
Q

Animal Tumor viruses that inactivate RB

A

HPV E7 and SV40T antigen

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9
Q

HPV proteins in HeLa cells that allow unlimited proliferation

A

HPV E7–> inactivates RB

HPV E6–>inhibits p53

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10
Q

Other cancers involving Retinoblastoma protein

A
  • Survivors of RB w/inherited susceptibility have a higher chance of developing a second, neoplasm, usually mesenchymal (ie osteosarcoma)
  • many small lung tumors and some breast tumors carry RB mutations
  • Rb KO mice have pituitary tumors with 100% penetrance
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11
Q

Events leading to loss of heterozygosity

A

Chromosome loss
Duplication of oncogenic chromosome
Rearrangements
Local events

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12
Q

Sporadic vs. inherited retinoblastoma

A

Sporadic is highly likely to occur in only one eye–> It’s extremely unlikely that double KO will occur sporadically in both eyes.

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13
Q

Viruses that inactivate p53 and RB in humans

A

Adenovirus E1B and HPV E6 –> Major route to cancer!

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14
Q

G-Actin vs. F-Actin

A

G Actin= One strand helical filament

F Actin= Double stranded

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15
Q

Arp 2/3

A
  • Looks like an actin dimer
  • attaches to an actin monomer, which creates the trimer necessary for nucleation and creation of an actin strand.
  • Creates new filaments at angles –>Branched network!
  • key for cell motility
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16
Q

Formin (FH2)

A
  • Binds 2 actin monomers
  • long, parallel actin cable filaments
  • Key for cell division
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17
Q

Phalloidin

A

Extracted from death cap mushroom, binds and stabilizes F actin which leads to increased actin polymerization

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18
Q

Actin in epithelial polarity

A

Anchors Tight Junctions and Adherens Junctions ( Decreased association of AJ proteins with actin can lead to loss of cell to cell adhesion, a prerequisite for epithelial-to-mesenchymal (EMT) transition (cancer)
Also plays a key role in microvilli

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19
Q

Actin in Microvilli

A

Actin bundles form in the microvilli, with plus ends anchored in the apical protein cap.

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20
Q

Microvilli inclusion disease

A

Myosin V is mutated (like kinesin)

Loss of microvilli is observed

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21
Q

Binding of a given myosin head

A

10% of time attached to actin (ATP bound)

90% not. Works because of multiple heads. - too much binding would cause stiffness.

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22
Q

Cell motility (leading edge)

A

Arp 2/3 polymerize at head and grow. Protrusion of fillopodia ad lamellipodia is driven by polymerization of actin meshworks at leading edge

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23
Q

Cell motility (retracting edge)

A

Formin Filaments and Myosin 2 cause retraction

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24
Q

Rho GTPases

A

control cell migratory activity

Active when bound to GTP, inactive when bound to GDP

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25
Q

Cell motility in development

A

-Very important for neural crest cells, axons

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26
Q

Wiskott-Aldrich syndrome

A

x-linked immunodeficiency resulting from WASp mutation. symptoms include thrombocytopenia and infections. Symptoms may result from defective lamellipodia/platelt formation

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27
Q

Lissencephaly

A

Severe defect of brain development resulting in smooth cortical surface. Caused by loss of function of n-cofilin, an actin filament

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28
Q

Metastasis

A

Cell motility is key in allowing metastasis to occur

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29
Q

Actomyosin ring and cytokinesis

A

Active Rho (GTP bound) activates Formin (–> forms contractile ring) and activates kinase ROCK (phosphorylates myosin and activates it) Everything then contracts! (Formation is dependent on the rho’s that are attached to tips of astral MT’s)

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30
Q

4 examples of asymmetric cell division

A
  • RBC’s (nucleus moved to side and pinched off with actomyosin ring)
  • Megakaryocytes keep dividing but never undergo cyotkinesis (up to 128 n)–> efficient for platelet making
  • Sperm
  • Epithelial cell divisions (cells must divide along the long axis, not the short one
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31
Q

Paracrine vs. Autocrine

A 
Paracrine= local mediator, ligand sent out by one cell and detected by another receptor
Autocrine= receptor on the signaling cell itself
Endocrine= long distances, released in bloodstream
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32
Q

Signal termination (5 mxns)

A

1) Initiation by another signal (phosphorylation or dephosphorylation)
2) elimination of extacellular signaling molecule (diffusion, inactivation, uptake into cells by transporter)
3) Receptor - reduction of binding, receptor internalization
4) 2nd messenger removal (Ca2+ ATP-dependent pumps, cAMP and cGMP breakdown by PDE’s
5) Protein binding/targeting (lack of inducing stimulus, protein degradation)

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33
Q

Phosphodiesterase

A

cXMP–> XMP
PDE5 is for cGMP
Negative feedback- allosteric cGMP binds and enhances PDE, and cGMP activates PKG, which phosphorylates and activates PDE

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34
Q

Viagra mxn

A

PDE5 inhibitor
o NO stimulates guanylyl cyclase –> PKG activation –> reduces intracellular Ca levels –> smooth muscle relaxation –> vasodilation –> penile erection

A competitive pathway is cGMP breakdown and inhibiting PDE 5 favors that pathway

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35
Q

FAP and RB inheritance

A

autosomal dominant ssusceptibility

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36
Q

APC function

A

degrades any unbound, free beta catenin in the cytoplasm. When APC is lost, Unbound betacatenin goes to the nucleus to produce transcription of oncogenes (c-myc)

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37
Q

BRCA1 and BRCA2

A

key tumor suppressing behavior is DNA repair.

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38
Q

Fanconi’s anemia

A

Caused by homozygous mutation in BRCA2

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39
Q

p53 activity

A

p53 is a transcription factor that expresses genes that prevent cells from replicating damaged or foreign DNA. p53 is also required for apotosis

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40
Q

Viruses that inactivate p53

A

Adenovirus E1B and HPV (E6 protein)

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41
Q

What do gag pol and env encode? (From retrovirus genome)

A

gag= internal virion proteins, pol-=viral polymerase; env= virus emembrane glycoproteins (envlope proteins)

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42
Q

RNA genome

A

2 strands or RNA held together by a tRNA

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43
Q

Example v-onc segments

A

v-src, v-erb, v-abl, v-myc

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44
Q

v-src function

A

v-src codes for a kinase protein that phosphorylates tyrosine residues

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45
Q

v-erb function

A

Similar to EGFR structure, also a tyrosine kinase

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46
Q

v-abl

A

similar to tyrosine kinase found in human c=abl

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47
Q

differences between v-onc’s and c-onc’s

A

c-src has different carboxy terminal and introns than v=src; c-myc has additional introns

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48
Q

C-onc genes that can directly mediate cell transformation when introduced via retroviral promoters

A

some, not all. Ex. c-ras

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49
Q

Example supporting qualitative model of c-onc genetic changes

A

c-ras mutations in bladder cancer lead to a constituitively active protein (poor prognosis)

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50
Q

Examples of gene amplification in cancers (supports quantitative model)

A
  • N-myc is amplified in neuroblastoma, copy number is associated with prognosis (more is bad)
  • HER2/neu=ErbB2 –> amplified in 20% of breast cancers (encodes membrane protein kinase) (increased copy number=bad prognosis)
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51
Q

Herceptin

A

Monoclonal antibody for protein product of HER2/Neu/erbB2 oncogene (extend life in breast cancer!)

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52
Q

Gene therapy for RB

A

Injection of RB gene into a RB neg lung cancer cell inhibited tumorgenesis

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53
Q

E1b mutant adenovirus

A

Preferentially kills p53 mutated cancer cells because it can’t inactivate p53 and hence can’t kill WT cells.

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54
Q

Oncogene hypothesis

A

Why do drugs that inhibit “normal” cellular proteins (c-myc, c-abl, etc.) kill only the
cancer cells? One idea is that cancer cells but not normal cells have become dependent or
“addicted” to the overexpressed oncogene. This referred to as “oncogene addiction”

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55
Q

Li Fraumeni Geneics

A

Autosomal dominant
70% of cases associated with p53 mutation
40% of LFLS patients have o53 mutations

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56
Q

Li Fraumeni syndrome Diagnostic criteria

A

1) proband with sarcoma dx before age 45 AND
2) Primary relative with any cancer uner age 45 AND
3) A primary or secondary relative with a cancer before 45 or a sarcoma at any age

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57
Q

LFLS diagnostic criteria

A

1) Proband with any childhood cancer or sarcoma, brain tumor, or adrenal cortical tumor dx before age 45 and
2) Primary or secondary relative with a typical LFS cancer at ANY age and
3) Primary or secondary relative with any cancer before age 45

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58
Q

Genetic testing for Li fraumeni

A

Direct p53 sequencing. OR only include hot spots in exon 5-9

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59
Q

Functions of p53

A

-regulates protein and miRNA
-apoptosis
-cell cycle arrest in G1 o G2
Inhibition of angiogenesis and metastasis
DNA repair and damage prevention
mTOR inhibition, exosome secretion
p53 negative feedback
cellular senescence

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60
Q

DNA Damage and p53

A

ATM activates check 2 which activates p53
ATR activates Check 1 and p53. Chk 1 also interacts with p53.
p53 activates MDM2, which inhibits p53
MDM2 inhibits its activator, MDMX

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61
Q

cyclosporin

A

calcineurin inhibitor, immunosupressant
inhibits about 50% of all protein kinases
must bind immunophilin before it is active

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62
Q

rapamycin

A

mTOR (Ser/Thr kinase) inhibitor, immunosupressant
(mTOR and IL2 together activate CDK2, leading to T-Cell proliferation)
must bind immunophilin before it is active

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63
Q

4 sites likely to be distorted in the inactive state of a kinase

A
  • Activation loop
  • C-helix
  • Glycine-rich loop
  • ATP binding pocket
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64
Q

PKA

A

Inactive–> a pair of catalytic subunits is bound to a pair of regulatory subunits
Active–> cAMP binds to the regulatory subunit, releasing the catalytic subunit, which is phosphorylated automatically allowing it to catalyze rxns.

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65
Q

CDK2 Activation

A
  • Cyclin must bind
  • Phosphorylation required
  • Inhibitor must be removed
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66
Q

PDK1

A

Phosphorylates PKB and PKC to activate them

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67
Q

CAMKK

A

Phosphorylates CAMK1 and CAMKIV to allow it to be active when calmodulin binds

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68
Q

MAPK

A

MAPK is phosphorylated by MAPKK, which is phosphorylated by MAPKKK (great example of multiple layers of regulation by kinases)

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69
Q

VHL genetics

A

Autosomal dominant condition caused by a mutation in VHL tumor suppressor gene. Highly penetrant. 80% of cases are inherited, 20% are de novo.
Other alterations include BAP1, PRBM1,

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70
Q

VHL associated lesions

A
  • Cerebellar/spinal cord hemangioblastoma
  • Retinal hemangioblastoma
  • Pheochromocytoma
  • Pancreatic cysts and neuroendocrine tumors
  • Endolymphatic sac tumors
  • RCC’s
  • Genitourinary tumors
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71
Q

Dx of VHL

A

A) 1 VHL-associated lesion + family hx
2) 2 VHL-associated lesions
(RCC, HB, and PHEO are 3 that are particularly likely to merit a referral)

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72
Q

Type 1 VHL

A

Total or partial VHL loss (improper folding)
High risk of HB, ccRCC
Low risk PHEO

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73
Q

Type 2 VHL

A

missense mutation

high risk of PHEO

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74
Q

VHL gene

A

Tumor suppressor, part of a complex that targets proteins for ubiquitin mediated degradation
-regulates HIF, suppresses aneuploidy, stabilizes microtubules

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75
Q

ccRCC genetics

A

4% familial (VHL is the most common inherited type)

96% sporadic (solitary, unilateral, late onset)

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76
Q

3 therapies for RCC

A

1) Immunotherapy- High dosage IL2 upregulates immune response, which is depressed in RCC. High toxicity
2)VEGF inhibitor–> tries to prevent angiogenesis. AE’s: GI, HTN, fatigue
3) mTOR inhibitors
mTOR is upregulated in 20% of ccRCC’s

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77
Q

Cholesterol functions in membrane

A

increase membrane stiffness and thickness (equally distributed in exoplasmic and cytoplasmic layer)

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78
Q

Lipids on exoplasmic surface

A

Phosphatidyl choline, sphingomyelin, glycolipids

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79
Q

Lipids on cytoplasmic surface

A

Phosphatidyl inositol, Phosphatidyl serine, Phosphatidyl ethanolamine

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80
Q

Glucosylphosphatidylinositol (GPI)

A

Extracellular linker that attaches many proteins to the cell membrane

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81
Q

Cholesterol synthesis

A

Made from Acetate by a 30-step synthesis pathway. The first step is catalyzed by HMG CoA reductase, which is blocked by statins
Every enzyme has a sterol regulatory element (SRE) (A few aa’s where a regulatory protein can bind)

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82
Q

SREBP

A

A Protein containing a transcription factor that regulates both LDLR and all 30 uptake receptors. If cholesterol is low, the Transcription factor is cleaved in the golgi and released to the nucleus.
TF has a short lifetime

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83
Q

Location of Cholesterol senseing

A

ER! (it has the lowest cholesterol ER

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84
Q

SCAP

A

Regulates whether SREBP tf is cleaved and released. Insig binds SCAP to block CopII site when cholesterol is high, but when cholesterol is low insig is released and SREBP can be transported to the Golgi

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85
Q

S1P and S2P

A

2 Proteins that cleave the transcription factor. S1P–> luminal cut S2P==> membrane cut

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86
Q

Volumes of Intracellular and Extracellular fluids in a normal body

A

IC: 27 L
Extracellular= 18 L (13 L + 5 L “third space”)
Plasma= 3L

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87
Q

[Na+] in ICF and ECF

A

ICF: 14 mM
ECF: 140mM
Functionally impermeable due to pump

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88
Q

[K+] in ICF and ECF

A

ECF= 145 mM
ICF= 5 mM
Permeable

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89
Q

[Cl-] and [HCO3-]

A

ECF: Cl= 115 HCO3= 25 (145 total)
ICF: Total= 5 mM
Permeable

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90
Q

[big anions]

A

ECF: 0 mM
ICF: 126 mM
Not permeable

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91
Q

[H20]

A

ECF: ~55k
ICF: ~55k

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92
Q

[Ca++]

A

ECF: 1 mM
ICF: ,0001 mM

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93
Q

[H+]

A

ECF: ,00004 mM

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94
Q

max urine mosM

A

1200

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95
Q

Plasma osmolarity

A

300 mM

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96
Q

Osmotic pressure

A

=reflection coefficient * RT (change in concentration)
Coefficient=1–> nonpermeable
=0–> as permeable as water

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97
Q

Equivalents

A

number of “combining-weights” of an ion per liter; calculated by a two step process: for each ion – convert to mosM; multiply mosM by the valence of the ion

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98
Q

Tonicity

A

effect of a solution on a cell; depends on the permeability of the membrane; solution that makes cell shrink is hypertonic; solution that makes a cell burst is hypotonic

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99
Q

‘Third space’

A

Eyes, gut lumen, sweat glands, kidneys

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100
Q

Butolantoxin

A

Prevents NT vesicle fusion by cleaving SNARE proteins

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101
Q

Syntaxin

A

3 amphipathic helices with transmembrane domain at very end, on plasma membrane, not in middle

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102
Q

SNAP-25

A

Pamitoylation sequence gets fatty lipid attached which anchors it to the plasma membrane

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103
Q

VAMP

A

Sits on synaptic vesicle and helps with NT release into cleft, huge amphipathic helix in the middle.

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104
Q

NSF

A

A triple ATP-ase that disassembles the SNARES using alpha snap as an adaptor protein.
Every unwinding hydrolyzes 6 ATP’s

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105
Q

nsec1

A

Binds to stabilize syntaxin in the closed conformation. When it diffuses away nucleation is possible (NSec1= brakes)

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106
Q

Viral Envelope fusogenic protein

A

COOH side - Transmembrane domain
N side- fusogenic peptide (very hydrophobic) Typically buried in the proein, but when the conformation changes and FP gets activated it embeds in the host plasma membrane

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107
Q

Influenza envelope protein activation

A

pH ~6 automatically opens the FP

This typically occurs in a lysosome, where the pH is low

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108
Q

HIV envelope protein activation

A

Receptor binding activation!
FP is a 2 protein dimer: Gp120 and Gp41
Gp120 sits on top of gp41 and blocks it.
There is a receptor on T-cells that bind gp120 and change conformation allowing gp41 to initiate viral membrane fusion

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109
Q

Membrane potential determination

A

It’s all about relative permeability!!

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110
Q

Number of excess anions in a cell if Vm =-80 mV

A

For every 100,000 cations in a cell there are 100,001 anions

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111
Q

Nernst equation at body temp

A

E= 60/z*log(Cout/Cin)

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112
Q

Donnan’s rule

A

[K]o[Cl]o=[K]in[Cl]in

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113
Q

Sodium pump

A

3 Na out, 2 K in

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114
Q

Driving force on an ion

A

Driving Force = Vm – Eion

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115
Q

Law of Mass action

A

Le Chatlier’s principle

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116
Q

Acute Hyperkalemia

A

Just a small leakage of K+ can lead to hube problems (20-30 mV depol in heart cells–> cardiac arrest)

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117
Q

Causes of Acute Hyperkalemia

A

Trauma, crush injuries, burns, immunological attack of RBC’s leading to hemolysis

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118
Q

Treatment of acute Hyperkalemia

A 
dx: EKG to detect arrhythmias
C: Calcium (quiet abnormal rhythms)
B: Bicarb (alkalize blood-->reuptake)
Insulin 
Glucose (both more ATP to power pump)
Kayexelate- ion exchanger that binds and removes K+ ions
119
Q

Henderson Hasselbach

A

pH=pKa+log([A-]/[HA])

120
Q

Bicarb buffer pH calculation

A

pH=6.1+log([HCO3-]/0.03 PCo2

121
Q

Normal blood pH

A

7.4
Normal [HCo3-]=24 mmHg
pCo2= 40 mmHg

122
Q

Enzyme that H. Pylori uses to create a neutral pH

A

urease

123
Q

Buffering range of a weak acid

A

+/- 1 pH level away from pKa

124
Q

Symptoms that highly suggest DKA in a kid

A

rapid breathing, nausea, vomiting

DKA=> Diabetes, Ketones, (metabolic) acidosis

125
Q

Typical metabolic disturbances in DKA

A

Plasma gluc >200 mg/dL

venous pH

126
Q

Stimulus for insulin release

A
  1. Glucose enters cell
  2. Glucose undergoes glycolysis (metabolism), causing an increase in ATP
  3. ATP inhibits a K+ channel that allows K+ to exit cell; K+ builds up in cell
  4. Cell becomes depolarized (Vm becomes more positive)
  5. Depolarization activates voltage-gated Ca2+ channel in the plasma membrane
  6. Ca2+ flows in, causing release of secretory granules containing insulin into the circulation
127
Q

Insulin target sites

A 
Insulin makes you store energy
-	Liver
o	+ glucose uptake, glycogen synthesis (storage form of glucose) 
o	– gluconeogenesis
o	– ketogenesis
o	+ lipogenesis
-	Muscle
o	+ glucose uptake, glycogen synthesis
o	+ protein synthesis
-	Adipose
o	+ glucose uptake
o	+ triglyceride uptake
o	+ lipid synthesis
128
Q

Cerebral Edema mxn

A

In DKA, when attempting to return the plasma to normal, you give the patient fluids. However, there is a high osmolarity of fluid in the brain (with high levels of glucose, because of diabetes), and fluid doesn’t cross blood-brain barrier as quickly. Therefore, if you give patient too many fluids too quickly, water may travel across the barrier into the brain because of osmolarity differences –> brain swelling –> potential death or neurological damage.

129
Q

Symptoms of cerebral edema

A

Cushing’s triad (hypertension, bradycardia, irregular or agonal respirations
altered mental status
Treatment with mannitol

130
Q

Smoking and IBS risk

A

smokers–> increased risk of Crohns

Non-smokers–> increased risk of ulcerative colitis

131
Q

Crohn’s characteristics

A

-Disease in ileum, discontinuous, fistulas common, transmural, bloody stool is rare

132
Q

Ulcerative colitis characteristics

A

Colon, continuous disease, fistulas are rare, mucosal, hematochezia common

133
Q

Extraintestinal symptoms of IBS

A

pleuritis, nephrolithiasis, ankylosing spondylosis erythema nodosum

134
Q

IBD genes

A

NOD1, Th17 pathway, Autophagy genes

135
Q

Glucose Transporter

A

Facilitated diffusion -concentration maintained by converting glucose to glucose-6-phosphate

136
Q

Hypokalemia

A

Low extracellular K–> decrease Ek
cells want to release more K to equalize things, but ion channels close to prevent this.
Decreased K permeability moves Vm away from Ek
—-> overall effect= depolarization

137
Q

Primary active transport

A

Na/K pump
Proton transporter gets H out of cells
Ca transporter (out of cells)

138
Q

Secondary active transport

A

Cotransport–> same direction
Antiport/exchanger–> different directions
3Na+/Ca++ exchanger in heart can change directions
Na+/Amino Acid exchanger is electrogenic
In synaptic vesicles, there’s a primary proton pump (gets them out). Secondary active transporter brings neurotransmitters in as H concurrently leaks back in

139
Q

H+/K+ Transporter

A

There are several clinical situations that suggest the presence of a system that will exchange K+ for H+, and vice versa. For example, infusing K+ causes acidemia (the K+ is taken up by cells ‘in exchange’ for H+), and infusing acid causes hyperkalemia.
But it doesn’t exist!! There are other ways of explaining these phenomena using multiple transporters

140
Q

Kv channel

A

4 membrane spanning polypeptides
Each domain contains 6 alpha helices
S4: charge sensing (lys or Arg in every third position)
S5/S6/P-loop form ion conducting pathway and selectivity filter

141
Q

Nav/Cav

A

Similar to Kv, but 1 really long polypeptide with 4 transmembrane domains

142
Q

Ionotropic NT receptors

A

most are heteropentamers. Receptor moiety and ion channel are all part of the same protein

143
Q

Factors that influence ion channel selectivity

A

charge, size, dehydration, multiple binding states

144
Q

NMDA receptors

A

Tetramers, 2 subunits bind glutamate, 2 subunits bind glycine

145
Q

CLC channels

A

dimers, each subunit has a channel

146
Q

Aquaporins

A

Tetramer, each subunit contains a water pore

147
Q

Nav M and H gates

A

M gate= activation gate

H gate= inactivation gate

148
Q

Relative/ absolute refractory period

A 
Relative= has to do with residually active Kv channels
Absolute= H gate still closed
149
Q

TTX

A

Charged molecule, cannot cross membrane. Blocks Nav selectivity filter extracellularly, has no effect intracellularly

150
Q

Lidocaine

A
  • Protonated (physiological) form cannot cross membrane

- anesthetic that only binds when gates are open on intracellular side (no effect extracellularly)

151
Q

Apical/Basolateral

A 
Basolateral= towards interstitial fluid
Apical= towards "outside"
152
Q

Epithelial Na/K pump

A

Always on the basolateral membrane, drives most transport (Exception: Protons are moved by a primary active transporter)

153
Q

NaCl transport across epithelium (tight epithelium)

A

Sodium ions leak into the cell across the apical membrane, down their electrochemical gradient. They are then pumped out of the other side of the cell by the Na/K pump, across the basolateral membrane. This results in the net transport across the epithelium of a positive charge, and chloride follows passively, drawn by the electrical force. The net transport of NaCl produces an osmotic gradient, which in turn draws water along.

154
Q

Glucose/amino acid transport across epithelium

A

Na dependent secondary active transport (aka Sodium leak transport) (Los of Na+ in mucosal solution stops pumping)
Sugar/aa Sodium cotransporter captures some of the energy released as Na moves down its electrochemical gradient into the cell

155
Q

Tight or Leaky epithelium

A

Epithelium involved in massive amounts of transport are usually leaky
In leaky epithelium, chloride and water often leak between cells rather than going through cells

156
Q

Location of leaky epithelium

A

Tubules of kidney, GI tract (not involved in creating concentration gradients.)
Leaky epithelium also shorts electrical potential differences.

157
Q

Trans epithelial potential difference related to each membrane potential

A

PD = Vm(BL) – Vm(Ap)

i) all membrane potentials are written as the potential of the inside of the cell with respect to the outside (i.e., outside = zero)
ii) the transepithelial potential is written as the potential of the apical solution with respect to the basolateral (i.e., basolateral = zero)
iii) the cell is isopotential (all voltage drops are at membranes, so all lines showing electric potential in Fig. 2 are horizontal – no change over distance, except across membranes)

158
Q

Third mxn of salt absorption

A

Apical Na+ channel replaced by a K+/Na+/2Cl- transporter (all into the cell)

159
Q

Chloride channels important for salt secretion

A

Basolateral: 3 Na+/ 6 Cl-/ 3 K+ into cell
Apical: Cl- secretion channel (ex. CFTR)
Chloride drags Na+ and H20 along with it (mostly through intercellular shunts)

160
Q

Metabolic waste

A

15 mol/day (13.5 osmoles in a body at a time)
14.5 mol/15= CO2
Kidney does most of the rest
400/500 remaining mmoles= urea
49/500 mmoles= H+
30 mmoles are secreted by GI tract, mostly RBC products

161
Q

GI transporter specificity

A

L amino acids and D sugars are selectively absorbed
However, while most things are absorbed as broken down substances (amino acids, not proteins, etc.), botulinum toxin is absorbed as a whole protein (unknown why/how).

162
Q

Myelination diseases

A

In the CNS: oligodendrocytes are myelinated –> MS

In the PNS: Schwann cells are myelinated –> Guillame-Barre

163
Q

Effects of Demyelination on ion channels

A

Demyelination causes proliferation of sodium channels along the axon. Increased sodium entry into the cell slows conduction speed
Demyelination causes an increased in “naked” K channels along the axon.

164
Q

Potential MS treatment

A
  • sodium channel blockers= Phenytoin Flecainide
  • potassium channel inhibitors, keep K inside the cell and brings resting potential back towards normal= Dalfampridine
  • Target immune system directly (monitor carefully for infection)
165
Q

EBV infection and MS

A

-EBV (mononucleosis) infection greatly increases MS risk, but not all people with EBV get MS

166
Q

MS risk genes

A

HLA-DRB1 (strong association)

Rare variants of CYP27B1 (activates vitamin D)

167
Q

Disease effects of errors in Nucleocytoplasmic transport

A

Cancer (For example, if p53 or NfKB localization is messed up)

168
Q

When is asymmetry of the NPC established?

A

During the cell cycle

169
Q

Conservation of NP’s between species

A

The 3D architecture is highly conserved

170
Q

Where is most RAN GTP located? Ran GDP?

A

GTP-> Nucleus

GDP-> cytosol

171
Q

3d architecture of nuclear pore

A 
o	Central framework
o	Cytoplasmic filaments
o	Nuclear filaments
o	Membrane layer
•	Anchored into nuclear envelope
o	Scaffold layer
•	Links between the membrane & rest of pore complex; provides curvature
o	Barrier layer
•	Performs function of acting as a selective gate
172
Q

Nucleoporins (Nups)

A

~30 distinct proteins repetitively arranged in distinct sub-complexes in nuclear pore

173
Q

FG repeats

A

Phenylalanine Glycine repeats common in Nups

  • Some FG repeats are cohesive – make continuous transient interactions with themselves
  • Others (FXFG) are non-cohesive and actively repel each other
  • Create different domains to increase efficiency of trafficking through the pore
  • Can rapidly interact, associate, & dissociate – critical to trafficking process
  • These repeats comprise ~12% of total mass of pore complex
  • They can also bind with cargo in the pore – many hydrophilic molecules are excluded!
174
Q

3 ways to go through a NPC

A

1) Small hydrophilic molecules fit through small gap between barrier nups (size-filtering diffusion)
2) Amphiphilic molecules spontaneously migrate through the pore. This causes changes in surface hydrophobicity
3) Facilitated transport (via karyopherins, etc.)

175
Q

Karyopherins

A

aka importins or exportins
A receptor family that can interact directly with cargo and FG nups. **contains RanGTP binding domain
They are also adaptors with cargo selectivity. They form a heterodimer with an alpha subunit

176
Q

Karyopherin subunits

A

beta= cargo carrier

Alpha- adaptor protein

177
Q

Nuclear Localization Signal

A

-Must be exposed on surface of folded protein to be active
-Classic = KKKRK (Lysine and Arginine)
Consensus= K (R/K) X (R/K)

178
Q

Cse1

A

Binds to Karyopherin a/b plus RAN GTP and transports it accross NPC

179
Q

Ran GAP

A

hydrolyzes Ran GTP in the cytosol and causes dissociation

180
Q

of molecules hydrolyzed to move one cargo molecule across the nuclear molecule

A

2 GTP’s (1 for cargo receptor, one for adaptor molecule)

181
Q

mRNA export

A

can be both Ran dependent and independent

NXF1 and NXT1 are mrna/rrna transporters

182
Q

nuclear transport regulation (NPC)

A

NPC dilation (pore permeability)
Nup relocalization
Protein expression and stability - Nup degradation

183
Q

Nuclear transport regulation (transport receptor)

A

Expression: competition with importins for Nup binding sites

Sequestration : mRNA export factor inhibition

184
Q

Nuclear transport regulation (cargo)

A

o Posttranslational modifications (phosphorylation, methylation, etc.)
o Posttranscriptional modification (mRNA splicing, tRNA nuelcar maturation)
o Intermolecular or intramolecular interactions (NLS and NES masking by homo-oligomerization)

185
Q

BRCA2/RAD51 and Nuclear export

A

In heatlhy cells, BRCA2/RAD51 are localized to the nucleus because the NES is covered by other molecules in the complex. Mutation can cause continuous NES exposure, leading to genomic instability

186
Q

Example of NES intermolecular masking

A

NF-kappaB NES site is masked by 1-kappaB

187
Q

NES by affinity enhancement example

A

When NFAT is phosphorylated, the NES is exposed.

When it is dephosphorylated, the NLS is exposed.

188
Q

Six functions of the ER

A

1) Cholesterol regulation
2) Lipid synthesis (Smooth ER)
3) Protein synthesis (Rough ER
4) Ca++ storage
5) Protein folding and posttranslational modification
6) Quality control

189
Q

Signal Recognition Particle

A

Made of RNA and protein

binds signal sequences in polypeptides being translated and localizes them to the rough ER

190
Q

Steps of Co-translational Translocation following SRP binding

A
  1. Binding of SRP causes a pause in translation
  2. SRP-bound ribosome attaches to SRP receptor, which is bound to translocon, in ER membrane
  3. Translocon opens, allowing polypeptide chain through; translation starts again (SRP and SRPR dissociate, 2 GTP are phosphorylated)
  4. Signal peptidase cleaves signal sequence from protein
  5. Completed protein folds within the ER lumen
191
Q

Multiple transmembrane domains

A

Proteins made in Rough ER contain multiple Start/stop transfer sequences

192
Q

N-linked glycosylation

A

Sugars are added to asparagines on the inside of the rough ER

193
Q

Four functions of Golgi Apparatus

A

1) Synthesis of sphingolipids from ceramide
2) Additional, later posttranslational modifications of proteins and lipids
3) Proteolytic processing
4) sorting of proteins and lipids for post-golgi compartments

194
Q

3 Vesicular coat proteins and where they go

A

1) Cop 1 (Golgi–> ER), one part of golgi to another
2) Cop 2 (Er–> Golgi)
3) Clathrin (Golgi–> plasma and back) (bidirectional)
- located in trans golgi network

195
Q

Dynamin

A

Pinches off vesicles when they are mostly formed

196
Q

Coat protein assembly and disassembly

A
  • coat proteins bind to proteins that recognize target membrane protein & cargo protein
  • when the coat forms a vesicle, has the right cargo
  • almost as soon as this release, the coat proteins dissociate – then it can get targeted to another organelle, or for exocytosis
197
Q

KDEL receptor

A

Located in the Golgi apparatus, captures soluble ER proteins and targets them to the ER via COP 1
(in the neutral ER, proteins dissociate and KDEL returns to golgi)

198
Q

Congenital Disorders of Glycosylation clinical features

A

-Dysmorphic face, cutis laxa, iris defects, dry, scaly skin, cerebellar hypoplasia, abnormal fat distribution, frontotemporal dysgenesis

199
Q

Mannose 6 phosphate

A

targets soluble enzymes to lysosomes. Binds to receptor that is targeted to vesicles that fuse with the endosome

200
Q

Hereditary spastic paraplegia

A

50% of disease associated are associated with membrane trafficking

201
Q

key features of cholera

A
  • dehydration – peeing less, extremely thirsty, chapped lips
  • severe dehydration – skin turgor! (tenting; stays when pressure is removed)
  • sunken eyes
  • profuse, watery diarrhea (up to liters per hour)
202
Q

Cholera toxin A and B subunits

A

A subunit= Active subunit cleaves off of B subunit, enters cell and binds G-protein that turns on AC, which makes cAMP and turns on CFTR
B subunit= Transporter. Binds GM1 ganglioside receptor on cell membrane

203
Q

CFTR in cholera

A

cAMP activates CFTR, which opens and causes a massive efflux of chloride ions. This causes massive amounts of water loss – secretory diarrhea.

204
Q

Physiology of ORT

A

Relies on solute-coupled sodium cotransporters. Despite the fact that you’re losing chloride ions (and thus water), the thinking is that if you bring sodium, glucose, and other solute back across apical membrane, you can draw water back in.

205
Q

Factors that increase cholera susceptibility

A

Age (children more susceptible), hypocholrhydria, O blood type, prior immunity, CF gene

206
Q

Cholera vaccines

A

Dukoral, Shandriol

Require 2 doses, not available in the US

207
Q

2 major routes for small volume endocytosis

A

Clathrin pinocytosis (clathrin coated pits used by LDL receptor, transferrin)
Calveolae (no coat, just lots of calveolin aggregates.)
-Used by cholera toxin, folic acid

208
Q

Quality Control in the ER (4 mxns)

A

1) Optimal oxidizing environment for folding and oligomeric assembly
2)Folding enzymes (Erp57 is a thioreductase that makes S-S bonds)
3) Molecular chaperone ATPases
Ex. BiP in Hsp 70 family
4)Folding sensors hold unfolded protein in the ER until they fold or are shuttled to degradation

209
Q

HSP 70

A

–> helps protein to fold by binding exposed hydrophobic patches on incompletely folded protein

210
Q

HSP 60

A

Barrel shaped structure forms “isolation chamber” –> midfolded proteins are fed in to prevent aggregation and promote refolding.

211
Q

Proteasome complex

A

Cylindrical chamber, Beta subunit flanked by 2 alphas
Alpha subunits regulate entry into “death chamber”
Beta subunits are proteolytically active

212
Q

Ubiquitin Ligases

A

E1- binds ubiquitin

E2 and E3 attach ubiquitin to the substrate and add more ubiquitin

213
Q

How many ubiquitins are needed to target a protein for degradation?

A

4

214
Q

Ubiquitin and MHC

A

Interferon gamma induces transcription of 3 novel proteasome subunits that forme “immunoproteasomes” These proteasomes cleave peptides that go bind MHC I, and then are placed on extracellular surface for recognition

215
Q

Apoptosis events in Plasma membrane

A
  • Phosphatidyl serine flips from the inner leaflet to the outer leaflet (inner/outer distribution becomes equivalent via scramblase)
  • Phagoccytes recognize this and engulf dying cells
216
Q

zeiosis

A

“boiling” action of cell membrane in apoptosis

217
Q

Cytoplasm in Apoptosis

A

Cells rapidly shrink and lose 1/3 of volume in seconds. This action along with zeiosis usually tears cell into “apoptotic bodies”

218
Q

Nucleus in Apoptosis

A

defining morphological feature= collapse of nucleus.

Chromatin becomes supercondensed and forms beads because it gets snipped every few nucleosomes or so.

219
Q

Necrosis

A
  • occurs during ischemia.
  • Calcium crystals form inside mitochondria, which swell.
  • Pumps fail due to lack of ATP, cells well and burst–> releases intensely pro-inflammatory contents into extracellular space
220
Q

Apoptosis and inflammation

A

Cells die inside of a macrophage, so there aren’t any pro-inflammatory substances released
Macrophages that phagocytose apoptotic cells are not activated, in fact, TGF beta is released, which is anti-inflammatory

221
Q

Morphogenetic death

A

genetic death during development that is programmed into our cells. While you’re generating shape, you have cell death. (Produces digits on limbs, many neurons are pruned)

222
Q

Caspase 8 and 9

A

activate Caspase 3 in the intrinsic and extrinsic pathway, respectively

223
Q

Initiation of Intrinsic apoptosis

A
  • normally, mitochondrial membrane is “guarded” by Bcl family genes that associate with the mitochondrial membrane & are anti-apoptotic
  • Signal for apoptosis: pro-apoptotic factors move to mitochondria (Bim, PUMA) –> Caspase 9
224
Q

Initiation of extrinsic apoptosis

A
  • Cytotoxic (killer) T cell can initiate apoptosis in any other body cell
  • CTL expresses a Fas in it’s membrane, which interacts with the death receptor, Fas, that’s on every cell.
  • In the target cell, Fas interacts with FADD and then acivates caspase 8-> caspase 3
225
Q

FLIPs

A

proteins that compete with Caspase 8 for FADD binding but don’t have activity and prevent apoptosis (many viruses use v-FLIP’s!)

226
Q

Autophagy

A

How stuff is delivered to lysosomes for degradation

227
Q

Sequence that initiates chaperone- mediated autophagy

A

KFERQ

228
Q

Chaperone mediated autophagy

A

Proteins with specific sequence allow Hsc70 to bind. Then other proteins bind and it’s delivered to the lysosome

229
Q

Macroautophagy big picture

A

Signaling leads to formation of a double membrane vesicle that encapsulates a bunch of proteins and organelles (autophagasome) then fuses with the lysosome

230
Q

Things that induce macroautophagy

A

Nutrient starvation, growth-factor mediated starvation, exposure to drugs, rapamycin

231
Q

Vesicle Nucleation

A

The first step. Double membrane forms and a P13K complex assembles (“phagophore”)

232
Q

Expansion and cargo targeting

A

Phagophore becomes an omegasome and cargo is targeted by LC3II and p60 proteins (they bind to polyubiquitin, etc. etc.

233
Q

Vesicle closure and other steps of macroautophagy

A

vesicle closure –> autophagosome
Fusion with endosome –>amphisome
Fusion with lysosome–> Autolysosome

234
Q

Regulation of Autophagy

A

Achieved by ATG genes (regulation mostly converges on mTOR)

235
Q

Autophagy and apoptosis

A

1) share regulatory proteins (BclII)
2) capsases can cleave autophagy regulators, blocking autophagy (ex. becilin 1)
3) Autophagy can also lead to cell death, some chemo drugs might use this pathway (HDAC inhibitors)

236
Q

Microtubule structure

A

Polymers of heterodimers of alpha and beta tubulin (each is bound to GTP)

237
Q

Microtubule breakdown

A

Beta tubulin hydrolyzes GTP forming a little kink, then the filament bends backwards and breaks apart. This is prevented by the GTP cap

238
Q

MT severing proteins

A

cut MT in the middle–> there’s not a GTP cap anymore, so the MTs fall apart

239
Q

2 categories of Intermediate filaments

A

Cytoplasmic IF’s

Nuclear lamins

240
Q

Structure of intermediate filamnets

A

Subunit: central alpha helical domain forms a parallel coiled-coil with another monomer. Pairs then associate in a parallel fashion to form staggered tetramers. NOT polarized

241
Q

Centrosome

A

Composed of a pair of centriolees embedded in a matrix and nucleation sites for MT’s.
Nucleation sites are rings of gamma tubulin that anchor the MINUS ends of MT’s

242
Q

MT severing proteins

A

katanin, spastin, fidgetin, VPS4

All triple ATPases

243
Q

Drugs that modify MT polymerization

A

Colchine inhibits MT polymerization
Vinblastine and vincristine are MT polymerization blockers
All are derived from plants

244
Q

Dyneins

A

Towards (-) end (retrograde)

245
Q

Kinesins

A

Towards (+) end

coiled coil with head that binds to MT and tail that binds to adaptor protein/cargo

246
Q

Kinesin Cycle

A

ATP hydrolysis will change the conformation of the head domain, causing kinesin to take a “step” forward

247
Q

Hereditary spastic paraplegia

A

Loss of spastin effects axonal transport

248
Q

MT’s in mitosis

A

Kinetichore MT’s bind each sister chromatid but can’t generate force to separate them
Astral MT’s bind membrane on the sides
Overlap MT’s use double headed kinesins to pull sister chromatids apart

249
Q

Nuclear Laminas and Progeria

A

Caxx is a site where prenylations are added to make proteins membrane bound. This prenylation and cleavage are necessary for lamin function. Progeria mutation prevents removal, treatment is enzyme inhibition

250
Q

Keratin mutation

A

Epidermolysis bullosa
Most devastating keratinmutation is Keratin 8/18. The only keratin expressed in the liver eventually leads to liver failure

251
Q

Neurofilament mutations

A

interfere with axonal transport of neurofiliments and cause CMT syndrome
Abnormal neurofilament assembly may be involved in ALS

252
Q

Tyrosine kinase activation mxn

A

Ligand binding to receptor on extracellular side –> dimerization of receptors –> activates catalytic activity of the kinase –> autophosphorylation of tyrosine on cytoplasmic side

253
Q

Activation of Ras GTPAase by RTKs

A

Phosphorylation of tyrosines on receptor –> binding by Grb2 (using SH2 domain, which recognizes 3 aa on the receptor) –> binds Sos (a Ras GEF = GTP exchange factor. Binds to Grb2 using SH3 domain, which binds to prolines).Brings Sos to the plasma membrane, where it interacts with Ras –> activation by removing GDP, attaching GTP (GEF action)

254
Q

2 major classes of RTK-targeting cancer drugs

A

1) Antibodies block extracellular ligand binding and inhibit catalytic activity
2) TKI - blocks TKR kinase activity by binding in substrate (usually ATP)binding region of kinase

255
Q

Mxns of TKI resistance (EGFR as example)

A

1) Primary resistance- mutation is actually in Ras, so upstream inhibition won’t be as effective
2) Acquired resistance- a second site mutation in EGFR arises
3) Activation of other receptors like Met or ErbB2

256
Q

GPCR activation

A 
Upon ligand (agonist) binding, receptor catalyzes GDP dissociation (= rate-limiting step)
GTP then binds very quickly to nucleotide-free G α-subunit --> additional conformational changes --> active state of G-protein complex 
Active state = G-α-subunit-GTP dissociates from receptor & βγ-subunit --> effectors
257
Q

GPCR inactivation

A

α-subunit is a GTPase –> hydrolyzes bound GTP to GDP –> subunits reassociate & recouple to receptor

258
Q

B1 adrenergic signalling in heart

A

cAMP cascade
Agonists: NE, ep, isoproterenol
Antagonists: propanolol, metropolol ==> beta blockers, lower HR and BP

259
Q

Alpha 1 adrenergic signalling

A

PLC/ PIP2 pathway
Causes peripheral vasoconstriction, increasing blood pressure and shifting blooc away from skin
Agonists: NE, epi, phenylephrine
Antagonists: Prazosin (alpha blockers ALSO reduce bp)

260
Q

b2 adrenergic signalling

A

Like B1 but in the lungs
cAMP
cause smooth muscle regulation (bronchodilation)
Albuterol= agonist

261
Q

m2 cholinergic receptor

A

via Gi, counters Gs activity (suppresses AC)
Also activates GIRK, making membrane less excitable
antagonist= atropine

262
Q

m3 cholinergic receptor

A

PIP2/PLC
Causes bronchoconstriction
Antagonist: Ipratropium

263
Q

Receptor desensitization

A

-If a receptor is turned on for a long time GRK is activated, which phosphorylates the always on receptor. Beta arrestin then comes to bind and favors endocytosis of the receptors

264
Q

Heart failure

A

Elevated Epi/NE can cause downregulation of beta adrenergic receptor. Beta blockers can prevent over downregulation

265
Q

Rapamycin

A

Inhibits mTOR, which can no longer act on Cdk2–> prevents T Cell proliferation

266
Q

Cyclosporin

A

Inhibits calcineurin, which can no longer act on NFAT–> prevents proliferation of T cells
** Actually an inhibitor of ~50% of protein kinases (ATP binding site inhibitor)

267
Q

Glycine Rich loop of kinase structure

A

Gly-rich loop in small lobe clamps down and positions gamma phosphate in teh right position

268
Q

activation loop

A

a region on the large kinase lobe (most but not all kinases) that needs to be phosphorylated in order to work

269
Q

Cytoplasmic calcium buffers

A

ex. parvalbumin. control the spatial and temporal spread of calcium signalling

270
Q

ER/SR buffers

A

ex. Calsequestrin – allows large quantities of Ca++ to be stored without creation of a large gradient

271
Q

How does Ca2+ enter the cytoplasm?

A

-ion channels (vg and ligand gated) and store operated Ca2+ channels)

272
Q

Ca2+ moving from ER/SR into cytoplasm

A

IP3 receptors and ryanodine receptors

273
Q

Ca2+ extruded from cytoplasm to extracellular space

A

PCMA (ATPase)

Na+/Ca2+ exchangers move 1 Ca out for 3 Na in

274
Q

Ca2+ movement from cytoplasm to ER lumen

A

SERCA

275
Q

C2 domains

A

Calcium binding domains (Binding of Ca2+ to PKC activates it)
C2 domains are also important for Ca2+ etection by synaptotagmin, leading to vesice fusion

276
Q

EF hands

A

Calcium binding domains
Calumodulin had 4 EF hand domains. When calmodulin binds Ca, it can go bind other things (CAMK, etc. )
Also found in parvalbumin, troponin

277
Q

Intestinal stem cells and niche cells

A

Stem cells= CBC cells

Niche cells= Paneth cells

278
Q

Epidermolysis Bullosa

A

Missing Collagen type 7

Treatable with bone marrow transplant

279
Q

PDGFR alpha

A

a receptor in bond marrow that responds to HMBV1, a signal sent out by injured tissue, and promotes healing.

280
Q

Sources of Testosterone in body relevant to Prostate cancer

A
  1. Testes – 90-95% of systemic testosterone
  2. Adrenal glands – 5-10% of systemic testosterone
  3. Intracrine androgen production in the prostate cancer cells themselves
281
Q

Function of AR in prostate cancer

A

AR binds to androgen, usually testosterone, and upregulates transcription in the nucleus
Thus, by turning down expression of testosterone (orchiectomy, binding to androgen directly, etc.) the prostate cancer growth could be curbed

282
Q

4 sources of Androgen reduction treatment Insensitivity

A

1) Testosterone still made by adrenals binds AR
2) AR overexpression
3) AR mutation leading to promiscuous activation
4) Constituitive activation of AR ligand binding domain

283
Q

Abiraterone

A

a specific inhibitor of cyp 17 –> completely eliminates testosterone

284
Q

Enzalutamide

A

Binds to AR and inhibits nuclear translocation

285
Q

Glucosaminoglycans

A

GAG’s are proteins connected to a polysaccharide by a tetrasaccharide link
GAG’s may have just a few polysaccharides (ie decarin) or a ton( ie aggrecan)

286
Q

Heparin

A

a GAG that controls blood clotting

287
Q

Collagen in ECM

A

It is made from tropocollagen which is secreted by cells and cross linked by alkylases

288
Q

Fibronectin and Lamanin

A

2 other components of the Extracellular matrix
Signalling molecules
Fibronectin is a dimer, lamanin is a trimer

289
Q

Functions of GAG in the ECM

A
  • 3D scaffold/supporting matrix
  • Binds signalling molecules
  • create concenration gradients
  • slow leukocytes down in capillaries so that they can exit without being damaged
290
Q

MMP’s

A
  • Enzymes that cut through the ECM allowing cells to move thorough the ECM
  • Cells make an inactive form of MMP because intracellular MMP is bad (it cleaves lots of proteins). The inactive MMP is then secreted and activated by cleaving a c-terminal pro-domain.
  • MMP’s have specificity (ie one MMP might only cut collagen 4)
291
Q

Integrins

A
  • receptors in the plasma membrane that bind various ECM components (ie Fibronectin integrin binds only fibronectin)
  • Each integrin has an alpha subunit and a beta subunit. The area where they meet actually binds substrates
  • As cells move along, inegrins “treadmill”
  • most cells need to be attached to something or they will die
292
Q

E-Cadherins

A

Lateral adhesions to other cells

Each cell expresses some, when it encounters another cell’s Cadherin, they form a homodimer and bind together

293
Q

Selectins

A

bind to GAG’s and target cells to specific regions (this is why cancers metastasize to certain regions ex. breast->bone)

294
Q

2 methods of cell motility

A

elongation motility- cells send out pseudopodia and follow it
Blebs- Membrane sends out blebs and actin fills it in. favored in less dense ECM

Molecules to Medicine (5 decks)

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