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BMS2.18 Cell Junctions (ZHANG) > Cell Junctions and Adhesion > Flashcards

Cell Junctions and Adhesion Flashcards

1
Q

What are the three domains of an epithelial cell?

A
  • apical domain facing lumen
  • lateral domain connecting cell to other cells
  • basal domain sitting on basement membrane
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2
Q

What domains of the epithelial cell will you find cell junctions?

A

basolateral domains

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3
Q

What are the three major categories of junctions?

A
  1. occluding junctions
  2. anchoring junctions
  3. communication junctions
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4
Q

The six types of cell junctions:

A
  1. tight junctions (zonula occludens)
  2. belt desmosomes (zonula adherens)
  3. spot desmosomes (macula adherens)
  4. hemidesmosomes
  5. focal adhesions
  6. gap junctions
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5
Q

Function of tight junctions:

A
  • define cell polarity.
  • control passage of substances between adjacent cells.
  • belt-like distribution around the entire cell
  • associated with:
    • ACTIN
    • OCCLUDIN
    • CLAUDIN
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6
Q

Function of belt desmosomes:

(zonula adherens)

A
  • anchorage junction
  • belt-like distribution
  • associated with:
    • ACTIN
    • CADHERINS
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7
Q

Function of spot desmosomes:

(macula adherens)

A
  • anchorage junctions for lateral walls of cells
  • spot-like distribution
  • associated with:
    • INTERMEDIATE FILAMENTS
    • PLAQUE PROTEINS
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8
Q

Function of hemidesmosomes:

A
  • link basal domain of cell to basement membrane
  • composed of intermediate filaments associated with a plaque
  • associated with:
    • INTEGRINS
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9
Q

Function of gap junctions:

A
  • allows cells to communicate with one another
  • composed of connexons​​
    • ​connexons are channel-like structures that allow the passage of small molecules between cells.
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10
Q

What two proteins mediate tight junction adhesion?

A
  1. occludin
  2. claudins

BOTH ARE TRANSMEMBRANE PROTEINS

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11
Q

What is this an image of, and what are the black arrows pointing to?

A
  • image = tight junction
  • arrows = kissing points
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12
Q

What is this a picture of, and what are the black arrows pointing to?

A
  • image = EM of a tight junction
  • arrows = “sealing strands”
    • where the two membranes are tightly linked together by lines of transmembrane proteins.
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13
Q

Occludins and claudins are linked to the actin cytoskeleton through:

A
  • adaptor proteins; ZO-1
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14
Q

Apical constriction and invagination are carried out by:

A

belt desmosomes

  • important during development
    • i.e. neural tube formation
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15
Q

Order of junctions from the apical surface of a cell to the basal surface:

A
  1. tight junction
  2. belt desmosome
  3. spot desmosome
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16
Q

Cadherins:

A
  • transmembrane proteins that mediate adhesion at the belt desmosomes
  • require calcium to function
    • can bind four calcium ions
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17
Q

Cadherins are linked to the actin cytoskeleton via:

A
  • catenins
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18
Q

The extracellular domain of cadherins consists of:

A
  • four domains
    • each binds to a calcium ion
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19
Q

E-cadherin:

A
  • mediates cell-cell adhesion at belt desmosomes
  • prerequisite for tight junction formation
  • lack of supports metastasis in cancer
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20
Q

What protein engagement is a prerequisite for formation of tight junctions?

A
  • E-cadherin engagement in belt desmosomes
    • must occur before tight junction formation
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21
Q

Loss of what protein leads to epithelial-mesenchymal transition (EMT; metastasis) during cancer progression?

A
  • E-cadherin
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22
Q

What is this an image of?

A

spot desmosome

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23
Q

What two proteins adhere spot desmosomes together in the cytoplasm?

A

desmocollins and desmogleins

BOTH ARE FROM CADHERIN FAMILY

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24
Q

What proteins make-up the dense cytoplasmic plaques of spot-desmosomes?

A

DPP

  1. desmoplakin
  2. plakoglobin
  3. plakophillin
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25
Q

Spot desmosomes are anchored to:

A

intermediate filaments

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26
Q

What are the black arrows pointing to?

A

spot desmosomes in LM

“ladder-like” appearance

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27
Q

What is this an image of?

A

spot desmosomes

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28
Q

What to types of junctions anchor the basal surface of a cell?

A
  1. hemidesmosomes
  2. focal adhesions
29
Q

Integrins:

A
  • two subunit transmembrane proteins present in both hemidesmosomes and focal adhesions on the basal surface of cells
  • bind to both extracellular matrix and internal cytoskeleton
30
Q

Structure of integrins:

A
  • two subunits (alpha and beta)
31
Q

Integrins interact with what intracellular (cytoplasmic) proteins?

A
  • in focal adhesions = actin
  • in hemidesmosomes = intermediate filaments
32
Q

Integrins interact with extracellular matrix proteins via:

A
  • an RGD peptide sequence that binds to fibronectin and laminin.
    • RGD =
      • arginine
      • glycine
      • aspartic acid
33
Q

What is this an image of?

A
  • hemidesmosomes
    • look like ½ a spot desmosome
34
Q

What protein mediates the interaction of cells and the basement membrane via hemidesmosomes?

A
  • integrin α6β4
  • hemidesmosomes are linked to intermediate filaments on the cytoplasmic side
35
Q

Hemidesmosome adhesion protein, plaque protein, and cytoskeletal protein:

A
  • adhesion: integrin α6β4
  • plaque: plectin, BPAG 1
  • cytoskeletal: intermediate filaments
36
Q

Spot desmosome adhesion protein, plaque protein, and cytoskeletal protein:

A
  • adhesion: cadherins (desmocollin, desmoglein)
  • plaque: desmoplakin, plakoglobin, plakophilin
  • cytoskeletal: intermediate filaments
37
Q

Focal adhesions adhesion protein, plaque protein, and cytoskeletal protein:

A
  • adhesion: integrins
  • plaque: vinculin, talin
  • cytoskeletal: actin
38
Q

Belt desmosomes adhesion protein, plaque protein, and cytoskeletal protein:

A
  • adhesion: cadherins
  • cytoskeletal: actin
39
Q

The two cell-cell anchoring junctions:

A
  • belt desmosomes
  • spot desmosomes
40
Q

The two cell-matrix anchoring junctions:

A
  • hemidesmosomes
  • focal adhesions
41
Q

Focal adhesions are not visible under conventional EM, but can be visualized using:

A

immuno-EM

42
Q

Function of focal adhesions:

A
  • important for cell signaling and cell migration
  • need functioning focal adhesions to have functional hemidesmosomes
43
Q

Gap junctions mainly serve to:

A

coordinate cellular responses

44
Q

Gap junctions are formed by:

A
  • connexon channels, which allow small molecules like Ca2+ and cAMP to pass from cell to cell.
45
Q

Connexon channel structure:

A
  • formed by six connexin proteins
  • connexons on cells interact with each other to form a hydrophilic channel between the two cells
46
Q

Connexon permeability is regulated by:

A
  • multiple factors, including:
    • pH
    • voltage
    • calcium
47
Q

What is this an image of?

A

EM of gap junction

  • the two plasma membranes are close together, similar to tight junctions. However, unlike tight junctions, gap junctions can be
    very extensive structures.
48
Q

What is this an image of?

A

clustering of connexons in a gap junction

(freeze-fracture EM)

49
Q

What two cell junctions have large extracellular domains?

A

belt desmosomes and spot desmosomes

  • makes sense - they have to find each other and bind first before tight junctions and gap junctions can form
50
Q

What type of junction is this?

A

gap junction

51
Q

What type of junction is this?

A

tight junction

52
Q

What type of junction is this?

A

belt desmosome

53
Q

What type of junction is this?

A

spot desmosome

54
Q

Claudin 16 mutation:

A
  • tight junction mutation
  • autosomal-recessive renal disorder:
    • hypomagnesemia
    • hypercalciuria
    • nephrocalcinosis
55
Q

P-cadherin mutation:

A
  • belt desmosome mutation
  • early hair loss
  • progressive degeneration of the central retina
56
Q

Defects in what types of junctions will cause blistering diseases?

A
  • hemidesmosomes
  • spot desmosomes

DUE TO AN AUTOIMMUNE DISEASE

57
Q

Pemphigus:

A
  • autoimmune disease with antibodies against desmoglein 1
  • defect in spot desmosomes
  • chronic blistering
58
Q

Pemphigoid:

A
  • autoimmune disease with antibodies against BPAG 1 and 2
  • defect in hemidesmosomes
  • chronic blistering
59
Q

Spot desmosome defects will cause splitting (blisters) where?

A
  • within the epidermal cell layers
  • due to pemphigus
    • autoimmune to desmoglein 1
60
Q

Hemidesmosome defects will cause splitting (blisters) where?

A
  • between the epidermis and the underlying basement membrane
  • due to pemphigoid
    • autoimmune to BPAG 1 and 2
61
Q

Non-Junctional Adhesion Mechanisms are usually found where?

A
  • during cell locomotion
    • dynamic cell-cell and cell-matrix adhesions are needed for locomotion
62
Q

Leukocyte extravasation is:

A
  • movement of white blood cells from the capillaries to the tissues surrounding them
63
Q

What adhesion proteins are needed during leukocyte extravasation during the inflammatory response?

A
  • Selectins
  • Immunoglobulin superfamily (IgCAMs)
64
Q

Selectins:

A
  • transmembrane proteins.
  • carbohydrate recognition domain that binds oligosaccharides.
  • REQUIRE CALCIUM.
  • Expressed on the surface of lymphocytes, endothelial cells and platelets.
65
Q

Immunoglobulin superfamily cell adhesion molecules (IgCAMs):

A
  • present on endothelial cells
  • have Ig-like domains on the extracellular side.
  • DO NOT REQUIRE CALCIUM.
  • ICAM and VCAM important for homing process.
66
Q

ICAM and VCAM:

A
  • two IgCAMs
    • present on endothelial cell surfaces
  • important role in the homing process of leukocytes
67
Q

Full Leukocyte extravasation process:

A

Selectin phase:

  1. Endothelial cells upregulate selectin and IgCAMs.
  2. Selectin has loose adhesion with leukocytes in blood.
  3. Leukocytes start rolling.

Integrin phase:

  1. While rolling, leukocytes activate integrins.
  2. Integrins bind to ICAM and VCAM on endothelial cells.
  3. Leukocytes arrest on endothelial cell surface.
  4. Integrin-mediated migration of leukocytes through the wall of the blood vessel, in between the endothelial cells.
68
Q

The two phases of the leukocyte extravasation process:

A
  • selectin phase
    • selectin slows down leukocyte
  • integrin phase
    • integrins arrest leukocyte

BMS2.18 Cell Junctions (ZHANG) (2 decks)

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