Exam 3 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

extracellular matrix (ECM)

A

fills the space between cells and binds cells and tissues together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

tissues are mosty ___

A

ECM and cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

different ECMs have ___

A

different types/proportions of fibrous proteins, polysaccharides, adhesion proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

basal laminae ECM

A

supports endothelial cells from beneath them;
surrounds muscle cells, fat, and peripheral nerves;
thin/sheet-like;
secreted by endothelial cells or epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

connective tissue ECM

A

(bone, tendon, cartilage, adipose, blood) is mostly ECM;
secreted by fibroblasts;
differ in proportions of proteins and polysaccharides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

connective tissue:
adipose ECM

A

less fibrous, mostly ground substance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

connective tissue:
tendons ECM

A

mostly fibrous, less ground substance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

connective tissue:
cartilage ECM

A

contains lots of polysaccharides for cushion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

connective tissue:
bone ECM

A

is hardened by calcium phosphate crystals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

fibrous, secreted proteins

A

include collagen and elastin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

fibrous, secreted proteins:
collagen

A

rope-like triple helix structure;
made of Gly-X-Y repeats;
forms two structures in ECM:
fibril-forming collagen (more rigid) and network-forming collagen (more flexible, less Gly-X-Y repeats)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

fibrous, secreted proteins:
elastin

A

cross linked structure to form network of elastic fibers that stretch and return to original shape;
expand AND contract;
important in arteries and lungs (which need to expand and contract)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

polysaccharides

A

glycosaminoglycans (GAGs) and proteoglycans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

polysaccharides:
glycosaminoglycans (GAGs)

A

repeated units of disaccharides;
NAG sugar + acidic sugar;
negatively charged, bind + ions to trap water and form hydrated gels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

polysaccharides:
proteoglycans

A

core protein with up to 100 GAGs attached at serine residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

adhesion proteins

A

link ECM components together and to cell surfaces;
include fibronectin and laminin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

adhesion proteins:
fibronectin

A

organize stuff in connective tissues with binding sites to link collagen, proteoglycans, and cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

adhesion proteins:
laminin

A

organize stuff in basal laminae with binding sites to link nidogen (binds collagen), proteoglycans, and cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

interactions between cells and the ECM

A

integrins;
modifying the ECM (MMPs);
growth factors;
cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

interactions between cells and the ECM:
integrins

A

heterodimeric transmembrane proteins that anchor to/connect ECM and cytoskeleton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

interactions between cells and the ECM:
modifying the ECM (MMPs)

A

matrix metalloproteases (MMPs) digest collagens, laminin, and adhesion proteins;
include heparanase and hyaluronidases that degrade GAGs;
heparanase expression usually limited to platelets/immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

interactions between cells and the ECM:
growth factors

A

proteins that regulate cell proliferation, migration, and survival/apoptosis;
bind to cell surface receptors and heparan sulfate proteoglycan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

interactions between cells and the ECM:
cancer

A

cancer cells show heparanase expression;
penetration of basement membrane = invasion and metastasis;
liberation of bound growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

cell adhesion molecules (CAMs)

A

help cells recognize each other and their environment;
cell-matrix adhesion molecules;
cell-cell adhesion molecules, many are transmembrane proteins, stable and transient interactions, many are Ca2+ and Mg2+ dependent;
homophilic and heterophilic binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

types of cell adhesion molecules (CAMs)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

cell-cell adhesion is ___

A

selective;
dissociated cells re-aggregate with cells of the same origin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

cell-cell adhesion dissociation by ___

A

trypsin (proteolytic enzyme) and EDTA (removes Ca2+ and Mg2+) destroys protein-protein interactions that hold cells together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

stable cell-cell adhesion

A

cells are not just passively clumped together;
tight junctions;
adherens junctions and desmosomes;
gap junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

stable cell-cell adhesion:
tight junctions

A

maintain polarity and barrier function in endo and epithelial cells;
claudins and occludins;
barrier function;
apicobasal polarity;
not very adhesive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

stable cell-cell adhesion:
tight junctions claudins and occludins

A

homophilic binding;
link to cytoskeleton inside cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

stable cell-cell adhesion:
tight junctions barrier function

A

between plasma membranes of adjacent cells;
blood brain barrier;
zo connects claudin/occludin to actin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

stable cell-cell adhesion:
tight junctions apicobasal polarity

A

active transport of glucose by intestinal epithelial cells from apical domain to basolateral domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

stable cell-cell adhesion:
tight junctions not very adhesive

A

so need help from adherens and desmosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

stable cell-cell adhesion:
adherens junctions and desmosomes

A

indirectly link the cytoskeletons of adjacent cells;
cadherins, classical and desmosomal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

stable cell-cell adhesion:
adherens junctions and desmosomes - cadherins

A

Ca2+ binding increases rod like structure in extracellular domain;
homophilic binding;
classical and desmosomal;
decrease in Ca2+/cadherin mutations cause dead embryos (8-16 cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

stable cell-cell adhesion:
adherens junctions and desmosoms - classical cadherins

A

anchored intracellularly by catenins to actin filaments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

stable cell-cell adhesion:
adherens junctions and desmosomes - desmosomal cadherins

A

anchored intracellularly to intermediate filaments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

stable cell-cell adhesion:
gap junctions

A

provide direct cytoplasmic connections between adjacent cells;
connexins and connexon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

stable cell-cell adhesion:
gap junctions connexin and connexon

A

6 connexins form hexamer with channel called connexon that aligns with another cells connexon to form gap junction;
pore for ions and small molecules to diffuse (cAMP, Ca2+, ATP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

transient cell-cell adhesion

A

cells with nomadic lifestyle and interact transiently (like WBCs);
selectins (inflammation);
integrins (Ig superfamily CAMs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

transient cell-cell adhesion:
selectins

A

bind cell surface carbohydrates;
L-selectin: WBCs;
P-selectin: platelets;
E-selectin: inflammation activated endothelial cells

42
Q

transient cell-cell adhesion:
inflammation

A

endothelial cells express E-selectin then bind to carbohydrates on WBCs and platelets;
initially weak interactions rolling along endothelium until integrins come to help

43
Q

transient cell-cell adhesion:
integrins

A

expressed by blood cells;
bind strongly to endothelial CAMs to allow tissue entry between endothelial cells;
immunoglobulin (Ig) superfamily CAMs

44
Q

transient cell-cell adhesion:
integrins Ig superfamily CAMs

A

biggest gene family in human genome;
extracellular Ig domain;
transmembrane and GPI-anchored;
homophilic or heterophilic binding;
abundant in immune and neural tissues (ICAM, NCAM)

45
Q

cell-cell adhesion modification

A

neural tube formation;
cell migration during development;
synapse formation during development and remodeling

46
Q

cell signaling scheme

A

ligand from one cell (transport and type);
received by target cell (location of receptor);
intracellular events (fast vs slow changes);
change in cell function (reversible vs irreversible)

47
Q

methods of cell signaling

A

juxtacrine (direct);
endocrine;
paracrine;
autocrine

48
Q

juxtacrine

A

direct contact between cells, does not depend on diffusion of the ligand;
gap junctions (metabolic or electrical coupled);
two forms of ligands: secreted ECM molecules or ligand on surface

49
Q

juxtacrine:
secreted ECM molecules (ligand)

A

integrins (receptor);
migrating cells travel via ECM molecules (like roads)

50
Q

juxtacrine:
ligand on surface (ligand)

A

CAM or cell surface receptor (receptor);
notch signaling in many developmental processes, disrupted in many cancers

51
Q

endocrine

A

hormones secreted by endocrine cells travel to target cells via circulatory system;
target cells must express the receptor;
two types of ligands: peptide hormones and lipid-soluble steroid hormones

52
Q

endocrine:
peptide hormones (ligand)

A

bind to cell surface receptors (receptor);
include insulin, FSH, prolactin;
synthesized as longer propeptides in ER, cleaved to active form in golgi, packaged into secretory vesicles and released

53
Q

endocrine:
lipid-soluble steroid hormones (ligand)

A

bind to intracellular (nuclear) receptors (receptor);
“nuclear” because most are transcription factors that change activity when signal arrives;
derived from cholesterol from ER;
include testosterone, estrogen, progesterone, corticosteroids, thyroid hormone, vitamin D3, retinoids

54
Q

paracrine

A

molecules secreted by cells into immediate environment;
diffusion and degradation;
target cells must express the receptor;
synapses (neurotransmitters and neuropeptides);
growth factors (steroid hormones and peptides)

55
Q

paracrine:
synapse - neurotransmitters (ligand)

A

typically ligand-gated ion channels (receptor);
they are hydrophilic;
include acetylcholine, GABA, glutamate, dopamine, etc

56
Q

paracrine:
synapse - neuropeptides (ligand)

A

cell surface receptors (receptor);
synthesized as polypeptides in ER, cleaved to active form in golgi, and secreted;
include NPY, endorphins, somatostatin, etc

57
Q

paracrine:
growth factors (ligand)

A

cell surface receptors (receptor);
regulate proliferation, differentiation, and survival BUT without being directly energetic;
include steroid hormones and peptides;
some work through paracrine, BUT also can be endocrine or autocrine

58
Q

paracrine:
growth factors (ligand) - peptides

A

most are synthesized in the ER, post-translationally modified, and shipped out by the golgi in secretory vesicles;
some cytokines;
include hedgehog family, WNT family, etc

59
Q

autocrine

A

molecules secreted by cell into immediate environment BUT affects itself;
feedback loop;
cancer

60
Q

autocrine:
feedback loop

A

to regulate the secreting cell’s signal

61
Q

autocrine:
cancer

A

cancer cells can use autocrine signaling to respond to their own cues

62
Q

signal transduction

A

transmits the chemical or physical signal from the surface to the cell interior

63
Q

G protein coupled receptors (GPCRs)

A

largest family of cell surface receptors, found in all euks;
transmembrane proteins with 7 membrane spanning α helices;
ligand binds at extracellular N-terminus or loops;
coupled to intracellular signaling pathways

64
Q

GPCRs:
ligand binds at extracellular N-terminus or loops

A

small molecules;
peptides;
fatty acids;
light

65
Q

GPCRs:
coupled to intracellular signaling pathways

A

cAMP pathway;
phosphatidylinositol pathway;
employ second messengers which trigger intracellular events (ligands are the first messengers)

66
Q

GPCRs are G protein coupled

A

rely on G protein cycle;
GPCR is bound to heterotrimeric G protein (α, β, γ);
1) ligand binds GPCR
2) GPCR cytosolic domain changes conformation - gets GEF activity (GDP to GTP, active)
3) α subunit and β/γ dissociate from each other and GPCR (interact with their target enzymes and ion channels)
4) RGSs (regulators of G protein signaling) stimulate GTPase activity of α subunit - gets GAP activity (GTP to GDP, inactive, association with GPCR and β/γ subunits)

67
Q

hormonal activation of adenylyl cyclase to create cAMP

A

galpha-s stimulates adenylate cyclase to increase cAMP;
galpha-i inhibits adenylate cyclase to decrease cAMP

68
Q

secondary messengers

A

levels affect the activity of downstream proteins;
protein kinase A (PKA);
cAMP regulates ion channels

69
Q

secondary messengers:
protein kinase A (PKA)

A

cAMP binds regulatory subunits of cAMP-dependent PKA (protein kinase A), catalytic subunits dissociate and phosphorylate targets

70
Q

cAMP

A

increases change activity of cytosolic pathways and nuclear pathways;
impacts skeletal muscle;
catalytic subunits of PKA liberate glucose and FAs and transcription of target genes

71
Q

cAMP:
catalytic subunits of PKA liberate glucose and FAs

A

1) catalytic subunits of PKA
2) phosphorylate phosphorylase kinase
3) phosphorylate glycogen phosphorylase
4) breaks down glycogen to glucose-1-P

72
Q

cAMP:
catalytic subunits of PKA transcription of target genes

A

1) catalytic subunits of PKA to nucleus
2) phosphorylates CREB (CRE-binding protein)
3) recruitment of co-activators to CREB bound at CREs (cAMP response elements)
4) transcription of target genes
*long term changes

73
Q

regulation of signal transduction

A

RSGs (regulators of G protein signaling);
cAMP phosphodiesterases;
phosphatases

74
Q

regulation of signal transduction:
cAMP phosphodiesterases

A

regulate secondary messenger levels

75
Q

regulation of signal trasnduction:
phosphatases

A

regulate levels of phosphorylation

76
Q

tyrosine kinases (TKs)

A

couple cell surface receptors to intracellular phosphorylation events;
tyrosine phosphorylation used for growth, cell survival, differentiation, metabolism;
ligand binds receptor, kinase activity, auto cross phosphorylation (at tyrosine residues)

77
Q

levels of phosphorylation downstream of TK signaling

A

tightly controlled;
protein tyrosine phosphatases remove tyrosine phosphorylation

78
Q

receptor TKs (RTKs)

A

transmembrane proteins with a single spanning α helix;
N-terminal;
C-terminal;
peptide growth factors;
activation

79
Q

receptor TKs (RTKs):
N-terminal

A

extracellular ligand-binding domain

80
Q

receptor TKs (RTKs):
C-terminal

A

cytosolic tyrosine kinase activity domain

81
Q

receptor TKs (RTKs):
peptide growth factors

A

send signals to many RTKs

82
Q

receptor TKs (RTKs):
activation for most

A

1) ligand binding
2) dimerization of receptor directly or by conformation changes
3) auto (cross) phosphorylation of receptor
4) increased TK activity (phosphorylation)

83
Q

receptor TKs (RTKs):
activation for most - increased TK activity

A

increased TK activity (phosphorylation) on cytosolic side and provides binding sites for additional proteins that bind to receptor with SH2 domains

84
Q

non-receptor TKs (nRTKs)

A

not transmembrane proteins but receive signals from cell-surface transmembrane receptors;
diverse structures;
activation;
cytoplasmic;
JAK/STAT signaling

85
Q

non-receptor TKs (nRTKs):
diverse structures

A

have diverse structures but ALL have catalytic domain with tyrosine kinase activity

86
Q

non-receptor TKs (nRTKs):
activation for most

A

indirect;
1) ligand binds non-catalytic receptor
2) activation of nRTK kinase activity
3) phosphorylation of receptor and/or autophosphorylation of nRTK
4) increased nRTK activity (phosphorylation) on cytosolic side and provides binding sites for additional proteins that bind to receptor with SH2 domains

87
Q

non-receptor TKs (nRTKs):
cytoplasmic

A

they are “cytoplasmic” in general but also anchored at membrane and nuclear envelope;
covalent lipid modifications anchor to plasma membrane;
non-covalently binds to receptors, other proteins, lipids;
SH2 domains;
integrin-binding domains (FAK family), integrins

88
Q

non-receptor TKs (nRTKs):
JAK/STAT signaling

A

downstream of cytokine receptors that receive cytokine and some peptide hormones (also downstream of GPCRs and RTKs with diff effects);
1) ligand binds cytokine receptor
2) receptor dimerization activates JAK (nRTK)
3) autophosphorylation of JAK
4) phosphorylation of cytokine receptors
5) SH2 of STAT proteins bind phosphorylation cytokine receptors
6) JAK phosphorylates STATs
7) STATs dimerize at SH2 domains
8) STAT dimer translocates to nucleus and affects gene expression as a transcription factor

89
Q

mitogen-activated protein kinase (MAPK)

A

signaling is a cascade of three protein kinases activated downstream of TKs (ERK, JNK, p38);
usually coupled to RTKs;
MAPK family members are serine/threonine kinases;
1) G protein activation by GEF
2) MAP3K activation by G protein
3) MKK activation by MAP3K
4) MAPK activation by MKK
5) target phosphorylation by MAPK

90
Q

MAPK signaling downstream of an activated TK:
GEF docking

A

1-3) RTK is activated by ligand binding and phosphorylated
4) GEFs dock at activated receptors with SH2 domains

91
Q

G protein activation

A

GEF docking at the activated receptor brings GEFs in proximity to membrane associated, small, monomeric G-proteins;
GEFs exchange GDP to GTP to active Rho or Ras;
GAPs activate GTPase activity to G protein hydrolyzes GTP to GDP to inactive Rho or Ras

92
Q

G protein activation:
MAPK signaling, G protein families

A

MAPK signaling is triggered by the activation of G proteins;
Ras family (ERK);
Rho family (JNK, p38)

93
Q

MAP3K (MKK kinase) activation

A

are activated by GTP bound G proteins;
1) GTP-Ras anchored at membrane recruits inactive Raf (MAP3K) from the cytoplasm
2) Raf links through Ras to PM
3) phosphorylation of Raf to active form with kinase activity

94
Q

MKK (MAPK kinase) activation

A

MAP3Ks phosphorylate MAPK kinases (MKKs) at serine/threonine residues;
1) inactive MEK (MKK) interacts with KSR (kinase suppressor of Ras) in the cytoplasm
2) activated Raf joins KSR/MEK and phosphorylates MEK

95
Q

MKK (MAPK kinase) activation:
KSR

A

KSR is a scaffolding protein that organizes components of the cascade;
ligand binding triggers recruitment of KSR/MEK to the plasma membrane

96
Q

MKK (MAPK kinase) activation:
MEK dual specificity

A

MEKs are dual specificity kinases - can work on serine/threonine residues AND tyrosine

97
Q

MAPK activation

A

MKK phosphorylation activates MAPK to phosphorylate at nuclear and cytoplasmic targets;
1) activated MEK (MKK) phosphorylates ERK (MAPK)
2) ERKs (MAPK) phosphorylate targets at serine/threonine residues

98
Q

MAPK activation:
ERK (MAPK) phosphorylation

A

cascade is specific - ERKs are the only physiological substrate of MEKs;
phosphorylated ERKs dissociate from KSR complex

99
Q

MAPK activation:
MAPK targets

A

activated ERKs anchor to cytoskeleton for transport to correct location;
some activated ERKs enter mitochondria (manage cell survival) and some enter nucleus (chromatin changes, nuclear import/export (NUPs of NPC), transcriptional activation and suppression)

100
Q

MAPK activation:
MAPK targets - nucleus transcriptional activation and suppression example

A

Elk-1 phosphorylation activates IEG (immediate early gene) expression;
IEGs (TFs) trigger downstream gene expression changes in SRGs (secondary response genes)