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MFM > Cell Adhesion and Membrane Junctions > Flashcards

Cell Adhesion and Membrane Junctions Flashcards

1
Q

difference between ECM in connective tissue and epithelia?

A

ECM is important for mechanical load in connective tissue, in epithelia, it is not important, as the cells are directly joined to each other and carry their own mechanical load

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2
Q

4 superfamilies of cell adhesion molecules?

A
  1. cell-cell adhesion 2. cell-matrix adhesion 3. calcium independent 4. calcium dependent
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3
Q

what proteins are responsible for cell-cell adhesion?

A

cadherins, Ig-like (I-CAMs), selectins

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4
Q

what proteins are responsible for cell-matrix adhesion?

A

integrins

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5
Q

what proteins are calcium independent?

A

Immunoglobulin like (I-CAMs)

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6
Q

which proteins are calcium dependent?

A

cadherins, integrins, selectins

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7
Q

what are I-CAMs

A

immunoglobulin-like cell adhesion molecule that are homophillic AND heterophillic, can interact with integrins (hetero) or other I-CAMs (homo)

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8
Q

examples of I-CAMs

A

N-CAM, VCAM-1, PECAM-1

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9
Q

what are N-CAM

A

neural CAMs, perform homophillic binding

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10
Q

what are VCAM-1s

A

vascular CAM, heterophilic binding

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11
Q

what are PECAM-1

A

platelet endothelial CAM, heterophilic binding

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12
Q

what are cadherin

A

family of calcium dependent, cell-cell adhesion molecules that contain cadherin repeats that bind to Calcium

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13
Q

what is E-Cadherin

A

epithelial cell

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14
Q

where is N-cadherin?

A

neural cell

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15
Q

where is P-cadherin

A

placenta and epidermis

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16
Q

what adhesion molecule makes up adherens junctions and desmosomes?

A

cadherin

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17
Q

what makes cadherin molecules (in the family) the same and different?

A

all have extracellular regions that have multiple copies of the cadherin domain motif, but the intracellular domains are varied (some can interact with components of the cells cytoskeleton aka actin)

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18
Q

general binding style of cadherin?

A

homophilic: specific subype on one cell bind to the same subtype on other cell

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19
Q

what occurs when cadherin is bound to calcium?

A

ca binds to hinge regions between the cadherin repeat domains and prevents the molecule from flexing, making cadherin rigid so it can associate with other cadherins

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20
Q

what happens when cadherin is NOT bound to calcium?

A

molecule is floppy and adhesion fails

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21
Q

which adhesion molecules are needed at synapses?

A

I-CAMs and cadherins, which are in both pre and post synaptic membrane and bind homotypically with one another. they are also bound to actin cytoskeleton in their respective cells (physical connection of cytoskeleton between the two cells)

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22
Q

what are integrins?

A

transmembrane heterodimers that redirect extracellular stresses from fragile plasma membrane to the sturdier cytoskeleton and help in signal transduction

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23
Q

what do integrin extracelllular domains bind to?

A

laminin, fibronectin, ICAM

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24
Q

what do integrin intracellular domains bind to ?

A

actin filaments via adaptor proteins

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25
Q

what is outside in activation?

A

binding of activation molecules on the extracellular domain of integrins can induce signaling events inside the cell

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26
Q

what is inside-out activation?

A

signaling cascades inside the cell can cause the tight association of integrin to molecules outside the cell

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27
Q

what determines integrin specificity of binding?

A

combination of their alpha and beta subunits ex. alpha5beta1 binds to fibronectin and if is mutated in either subunit leads to death of embryo

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28
Q

example of inside-out activation of integrin

A
  1. T-cell encounters an antigen presenting cell 2. cells first adhere weakly through integrin-ICAM interactions 3. when cells are close enough together, T-cell receptor binds to MHC-antigen complex 4. strong binding of T-cell receptor and MHC-antigen complex causes signaling event inside T-cell, activating intracellular tails of integrin 5. signal transmitted to extracellular domain, which results in the integrin binding more tightly to the ICAM
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29
Q

what is fibronectin?

A

large, multidomain protein that contains binding sites for collagen and integrins

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30
Q

function of the fibronectin-integrin complex?

A

provides a bridge between the ECM and the actin cytoskeleton of the cell

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31
Q

what are selectins and what are their roles?

A

they are cell surface carbohydrate-binding proteins (lectins) that direct white blood cells to sites of inflammation; each selectin has a lectin domain that binds to a specific oligosaccharide on another cell

32
Q

what are E-selectins?

A

found on endothelial cells and are induced by inflammation

33
Q

what are L-selectins?

A

found on leukocytes

34
Q

what are P-selectins?

A

found on platelets and endothelial cells

35
Q

how do selectins bind?

A

bind to glycans on the surface of other cells through its lectin domain, but the affinity for glycan is weak, making a weak adhesion between cells

36
Q

what is leukocyte extravasation?

A

the movement of leukocyte from the circulation to the site of tissue damage or infection

37
Q

4 steps of extravasation

A
  1. chemo attraction 2. rolling adhesion 3. tight adhesion 4. transmigration
38
Q

what occurs during the chemo attraction step of extravasation?

A

macrophages in affected tissue release cytokines (IL-1, TNFalpha) to attract leukocytes, which induces the expression of selectins on the surface of the endothelial cells lining the blood vessel

39
Q

what occurs during the rolling adhesion step of extravasation?

A

carbohydrates on the leukocyte plasma membrane bind to selectins on the plasma membrane of the endothelial cells lining the inner wall of the blood vessel - bind WEAKLY

40
Q

what occurs during the tight adhesion step of extravasation?

A

integrins on leukocytes bind to I-CAMs on the endothelial cells surfaces with high affinity and immobilize the leukocyte

41
Q

what occurs during the transmigration step of extravasation?

A

leukocyte passage through gaps between endothelial cells mediated by PECAMs (platelet endothelial cell adhesion molecules)

42
Q

pathology of leukocyte adhesion deficiency?

A

mutation in gene that encodes a component of integrins, so the leukocytes don’t make functioning integrins. THEREFORE the leukocytes cannot bind to ICAMs on the surface of endothelial cells lining the lumen of the blood vessels = defective tight adhesions and deficiency of recruitment of neutrophils to site of infections

43
Q

characteristics of leukocyte adhesion deficiency?

A

recurrent infections due to a deficiency in recruitment of neutrophils to sites of infection, lowering ability to fight infections

44
Q

where are epithelial sheets located?

A

they line all internal cavities and cover the external surface of the body

45
Q

polarity of epithelial sheets?

A

apical and basal

46
Q

what is the apical face of epithelial sheet?

A

free and exposed to air or watery liquid

47
Q

what is the basal facet of epithelial sheet?

A

rests on and is attached to the basal lamina

48
Q

what is the basal lamina?

A

connective tissue composed of collagen and integrin that provides adhesive sites for integrin molecules in the plasma membrane of the epithelial cells

49
Q

5 types of membrane junctions

A
  1. tight junctions 2. adherens junction 3. gap junctions 4. desmosomes 5. demidesmosomes
50
Q

what are membrane junctions?

A

protein complexes found on the plasma membrane that physically connect two adjacent cells in an epithelial sheet or just the epithelial sheet to the underlying basal lamina

51
Q

composition of tight junctions

A

claudins and occludins

52
Q

what are tight junctions?

A

transmembrane proteins arranged in strands along the line of the cell junctions to create a tight seal near the apical end of the cell

53
Q

function of the tight junctions (2)

A
  1. physically holds cells together 2. serves a barrier function (protective and functional barrier)
54
Q

protective barrier functions of tight junctions

A

prevents passage of molecules and ions through space between cells so materials must pass through the cells themselves (selective passage of molecules)

55
Q

functional barrier function of tight junctions

A

help cells maintain polarity by preventing lateral diffusion of membrane proteins between apical and basal/lateral surfaces

56
Q

composition of adherens junctions

A

cadherins and linker proteins

57
Q

function of cadherin in the adherens junctions

A

cadherin molecules on the plasma membrane of one cell binds to cadherins in the plasma membrane of neighboring cells (homophilic binding)

58
Q

function of linker proteins in adherens junctions

A

connect the intracellular domain of cadherin to the actin cytoskeleton

59
Q

function of adherens junctions

A

join adjacent cells, and form a ribbon around the whole cell usually near the apical end. usually found right next to a tight junction

60
Q

what are gap junctions?

A

channels spanning the plasma membranes of two adjacent cells that directly connects the cytoplasm of the two cells

61
Q

what do gap junctions allow to pass?

A

small water soluble molecules and ions, but can be opened or closed in response to extracellular signals

62
Q

building process of gap junction intercellular channels?

A

6 subunits of connexins arranged radially for form central channel “connexon”, then connexons are arranged end to end in adjacent cells to make gap junction

63
Q

specificity in gap junctions?

A

different subunits of connexins combined to make different gap junctions of different properties

64
Q

what is the permeability of gap juncitons?

A

they are not open continuously, they flip between open and closed, usually regulated by Ca

65
Q

how would a gap junction respond to an increase in intracellular Ca?

A

gap junctions will close

66
Q

what is the most common cause of genetic hearing loss in children?

A

mutations in the connexin 26 gene (GJB2) cause inactive gap junction in the cells of the inner ear, preventing flow between cells that is necessary for hearing

67
Q

what are desmosomes?

A

help attach 2 adjacent cells together and gives the cells mechanical strength to resist shear forces by linking keratin filaments of the 2 cells

68
Q

where are desmosomes found in cells?

A

on the lateral surface of the cell

69
Q

what is cytoplasmic plaque made of and where is it?

A

plakoglobin/plakophilin and desmoplakin, connects to cadherins and intermediate filaments on the INSIDE of the cell (binds together the intercellular tails of cadherins with the anchored keratin)

70
Q

what types of proteins link the plasma membranes of adjacent cells in the desmosome?

A

desmoglein and desmocollin in the cadherin family

71
Q

what are hemidesmosomes?

A

cell-ECM adhesions that attach epithelial cells to the underlying basal lamina

72
Q

composition of hemidesmosomes?

A

plaque that contains dystonin and plectin, which creates a bridge between collagen and laminin of the basal lamina and the keratin fibers inside the cell IS ASYMMETRICAL aka uses dystonin and plectin to connect keratin in the cell to collagen and laminin in the basal lamina

73
Q

difference between desmosomes and hemidesmosomes?

A

hemidesmosomes are on the basal lamina/basal cell surface (cell-ECM) and desmosomes are cell-cell adhesions

74
Q

what is bullous pemphigoid?

A

when epithelial sheets lose their connections to the underlying basal lamina, forming a space that fills with fluid, making a blister.

caused by autoimmune antibodies against dystonin, a component of the plaque of hemidesmosomes

75
Q

what is pemphigus foliaceus?

A

antibodies against desmoglein-1 cadherin molecule, affecting desmosome (adhesion between adjacent epithelial cells)

a space is created between the junctions that fills with fluid, making a blister

76
Q

what is pemphigus vulgaris?

A

antibodies made against desmoglein-3 cadherin molecule in desmosomes, reduces adhesion between adjacent epithelial cells

causes space, fills with fluid, blister

77
Q
A

MFM (39 decks)

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