MTC Exam III part III

Question 1

microfilaments

Answer 1

actin polymers. help form microvilli. involved in cell shape, contraction, and intracellular trafficking

Question 2

microtubules

Answer 2

made of tubulin and microtubule associated proteins. extend the length of the cell. important for mitotic spindle, cilia, flagella. major system of intracellular trafficking

Question 3

What kind of change is likely to lyse a RBC?

Answer 3

a dramatic change in surface area

Question 4

describe the “fishing net structure” of an RBC

Answer 4

short activin filaments and spectrin molecs are located below the plasma membrane
specrin is composed of triple alpha helical and beta subunits which associate in an antiparallel manner
they attach to ankynin complex, which attaches to band three (tm bicarb transporter)
spectrin als attaches to band 4.1R, which attaches to glycophorin C

Question 5

describe vertical interactions in rbc structure

Answer 5

spectrin/ankynin/band 3 interactions; spectrin/actin/band 4.1R GPC interactions

Question 6

hereditary spherocytes

Answer 6

cell shabe disorder with problems with vertical interactios of RBCs.
leads to spherical RBCs
autosomal dominant most of the time
less surface area
cells ge trapped in spleen
leads to hemolytic anemia, jaundice, and splenomegaly.
treatment: spleen removal (but probs with infection and iron/folate deficiency)

Question 7

heterotypic vs. homotypic CAMs

cis vs. trans interactions

Answer 7

CAMs: integral membrane proteins that help cells adhere to each other
homotypic bind cells of same cell type; heterotypic bind cells of different cell types
cis binds cells on the same plane of the cell membrane; trans on different planes

Question 8

4 types of junctions

Answer 8

anchoring junctions (structural integrity of tissues)
occluding (prevent traffic thru intercellular space)
channel-forming (enhance chemical and electrical coupling of cells)
signal relaying: enhance cell-cell communication

Question 9

classes of CAMs

Answer 9

cadherins, IG superfamily, integrins, selectins

Question 10

cadherins. structure and types

Answer 10

E, N, and P. single pass TM. N terminal is extracellular, C terminal interacts with actin cytskeletion via alpha or beta catenin. require Ca2+

Question 11

pemphigus vulgaris

Answer 11

autoimmune skin blistering from desmosomal cadherins
autoimmune response against desmoglein.
flaccid blisters

Question 12

bullous pemphigoid

Answer 12

auto antibidies agasint hemidesmosomes which attach cells to the basal lamina
deeper, tensor leisons than pemphigus vulgaris

Question 13

cell-matrix adhesion: outside in mechanism

Answer 13

ECM ligand biding causes integrin clustering. the active receptor conformation is straight out rather than folded. active form causes binding to a linker protein to the cytoskeleton

Question 14

muscular dystrophy

Answer 14

DGC complex normally spans the muscle cell membrane and connects actin to the cell membrane. dystrogylcan and other protiens for the DGC complex. mutations in the DMD gene on X chromsome lead to less dystrophin which leads to weakness and muscle wasting. death and neuropsyche complications possible

Question 15

convergent extension

Answer 15

change in cell packaging leads to movement

Question 16

ameboid migration steps

Answer 16

extension, adhesion, translocation

Question 17

describe how actin works wrt ameboid migration. include the proteins (2) that are critical for this process

Answer 17

globular actin is activated by ATP in nucleation process to form protofilaments
protofilaments bind to form d helical filaments
new actin is added to the plus side
ATP binds to the mins side
Arp2/3 complex and formins attach actin filaments to each other
Arp2/3 links the negative ends to the middle of other actin filaments to form a branched array
formins nucleate straight, unbranched filaments to each other.

Question 18

ameboid extension

include the protein family and activation details

Answer 18

actin polymerization pushes a part of cell forward
rearrachement of the actin cytoskeleton under the control of Rho family monomeric GTPases. GTPases normally inactive but are activated by membrane bound guanine nucleotide exchange factors (GEFs). once activated, they help control Arp2/3 and formins

Question 19

what proteins mediate the translocation step of ameboid migration?

Answer 19

myosin motors

Question 20

Kti/Steel: what is this? for what cells is it important? what might we see in a heterozygote?

Answer 20

example of a survival factor/receptor pair needed for cell migration. found in germ cells, blood cells, neural crest cells. receptor is kit, survival factor is steel. kit heterozygotes have piedbaldism and possible mast cell leukemia, germ cell and GI tumors

Question 21

describe the notch receptor structure and synthesis

Answer 21

single pass receptor. extracellular domains have lots of EGF-like repeats. synthesized in the golgi as a single peptide. then cleaved such that receptors are heterodimeric.

Question 22

notch signaling pathway: what is the ligand? what happens upon binding?

Answer 22

DSL ligands found on nearby cells
when ligand binds, notch receptor undergoes two more cleavages. this releases an intracellular tail that goes toth the nucleus to bind a TF called CSL, which is a transcriptional activator (without tail, CSL actively inhibits notch targets)

Question 23

alagille syndrome

Answer 23

JAG1 mutuation, which we thing is a DSL ligand
autosomal dominant
intraheptatic biliary hypoplasia leading to jaundice, cardiac probs, skeletal abnormalities/butterfly vertebrae, ocular abnormalities, facial abnormalities

Question 24

CADASIL

Answer 24

cerebral arteriopathy, autusomal dominant subcortical infarts, leukoencepalpathy. notch 3 mutation.

Question 25

TGF-beta receptors: type and structure

Answer 25

ser/thr kinases 2 types type II homodimers bind ligands, then recruti, phosphorylate, and activate type I homodimers to for a heterotetramer

Question 26

what happens upon ligand binding to TGF-b receptors

Answer 26

type II homodimers recurit and activate type I homodimers. together, they transduce they phosphorylate a smad. this smad associates with smad4. together, the smad complex goes to the nucleus and activates target genes

Question 27

What Smads mediate TGF transcription vs BMP?

Answer 27

Smad 2 and 3 is TGF; Smad 1,5,8 is BMP

Question 28

what are the 5 levels of TGF regulation

Answer 28

1. TGF secreted into ECM in inactive form and not activated without help of throbospondin 2. TGF antagonists exist 3. so do inhibitory smads (smad6 and smad 7) 4. co-receptors 5. receptor decoys: bind the receptor but don't trigger the pathway

Question 29

HHT/Osler-Rendu-Weber syndrome

Answer 29

heretiary hemorrhagic telangiectasia autosomal dominant vascular dysplasia, lung, liver, and brain involvement with lots of bleeds mutations in Eng, Alk1 or Smad4: probs with TGF-beta pathway

Question 30

From what to arterio/venous malformations result in HHT? (4)

Answer 30

1. loss of a/v identity in development 2. abnormal vascular remodeling 3. apoptosis of capillary epithelial cells 4. dilation of anastamsoes because of loss of vascular smoolth muscle.

Question 31

PAH: pulmonary artery hypertension

Answer 31

symptoms: SOB, increased R ventricular work and right ventricular failure problem with TGF-B signaling with BMP, whish is neeaded for early vasculogenesis.

Question 32

Marfan syndrome

Answer 32

affects ocular (myopia, displacement fof the lense, retinal detachment, glaucoma, cataracts), skeletal (bone overgrowth and jt laxity), and CV systems (aortic dilation and rupture, mitral valve prolapse, tricuspid valve prolapse). due to FBN1 mutations. caused by lack of fibrillin, which is needed in elastic and non-elastic tissues. And, FBN1 usually helps keep TGF-beta latent: FBN1 problems lead to over expression of TGFbeta signaling and excessive bone and aortic growth

Question 33

loeys-dietz syndrome

Answer 33

similar to marfan syndrome but due to TGFbeta receptor issues (aortic aneurysi, arachnodactyly, etc.

Question 34

from what are the limbs derived?

Answer 34

lateral plate mesoderm

Question 35

Which T box genes are critical in the legs? In the arms?

Answer 35

Tbx 4 in legs and 5 in arms

Question 36

describe proximal/distal limb growth orientaiton

Answer 36

controlled by AER (apical ectodermal ridge), which produces Fgfs 2,4, and 8. progress zone is proximal to AER and consists of undifferentiated mesenchyme. the longer the time spent in the zone, the more distal the bone. Fgf4 expression maintained by Shh from the ZPA

Question 37

describe dorsal/ventral specification of limb

Answer 37

dorsal identity determined by Wnt signalling pathway. Wnt indirect induces dorsal identity. ventral identity is the default (En1 signaling)

Question 38

anterior/posterior specification in limb

Answer 38

anterior: thumb; posterior: pinky controlled by zone of polarizing activity (ZPA) in the posterior region. ZPA confers posterior identity to limb cells using a Shh gradient ZPA specified by Hoxb8 gene and regulated by retinoic acid. Shh expression maintained by Fgf4 form AER and vice versa.

Question 39

Holt-Oram

Answer 39

TBX5 gene mutation leading to upper limb defects and congenital heart problems

Question 40

GLI-3 defects

Answer 40

lead to brain and hand malformations

Question 41

forebrain brain development: what determines anterior/posterior patterning?

Answer 41

Goosecoid from prechordal plate

Question 42

brain devo: what determines dorsal/ventral patterning in the brain?

Answer 42

two opposing gradients: ventrally, it is Shh expression; dorsally, it is BMPs together make a differential gradient

Question 43

holoprosencephaly definition

Answer 43

single cerebral ventricle

Question 44

SHH structure and synthesis

Answer 44

must be activated by an auto cleavage process. N-terminal signal seq is cleaved. the remaining peptide is cleaved into 2 halves by addition of acholesterol moiety to the C terminal of the half that was original the N terminal.

Question 45

SHH signaling

Answer 45

SHH activated (requires cholestero). Shh goes to surface receptor PATCHED (aka PTCH) PATCHED releases Smo, which carries out a signaling cascade in the cell

Question 46

general structure of a motile cilia

Answer 46

microtubule based organelle: 9+2 configuration | have hyneine and radial spokes

Question 47

structure of a non-motile cilia

Answer 47

9+0 config with no dynein arms

Question 48

What organelles are necessary for ciliogenesis? Where do they come from

Answer 48

basal bodies. can either come from mitosis or from generative complex/deuterosome

Question 49

What two proteins are important for intraflagellar transport system?

Answer 49

kinesin2 brings molecules to the cilia tip and dyneine2 brings stuff back

Question 50

how do motile cilia work?

Answer 50

sliding of the doublets against each other there is an A and B tubule in each doublet. dyneine arms extend form A towards B (inner and outer), and radial spokes connected dynein arms around the central microbutule. sliding of doubles in a ATP dependent fashion occurs

Question 51

Primary Cilia dyskinesia

Answer 51

autosomal recessive disorder characterized by chronic upper resp. infection and situs inversus

Question 52

nodal vesicular parcel model vs. 2 cilia model

Answer 52

two models to explain how cilia are important in left/right determination NVP: vesicles filled with Shh and retinoic acid are screted on the right side of the nod and are swept to the left via cilia. vesicles then open and cilia on the left of the node are chemical sensors 2 cilia model: motile cilia create a leftward flow sensed by left immotile cilia. cilia are mechanical sensors in this model.

Question 53

what two senses require cilia?

Answer 53

smell and sight (rods and cones)

Question 54

Bardet-Biedl syndrome

Answer 54

obesity, retinal rod/cone dystrophy, polydactyly, cog impairment, hypogonadism, UG malformation and nephropathy genes are involved in IFT, esp. in parts of the brain that control hunger

Question 55

Polycystic kidney diseases

Answer 55

autosomal dominant involving kidneys, liver, pancreas | primary cilia defects:

Question 56

pallister-hall syndrome

Answer 56

autosomal dominant hypothalamic probs, epiglottis, laryngeal cleft, pulmonary segmentation, polydacly caused by GLI-3 problems. GLI3 mediates SHH pathway thru distal IFT without SHH, GLIR represses SHH genes (retrograde transport of GLIR to cell body). with SHH, SMO is releases and transported to the tip such that GLIA predominates.