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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
Spot desmosomes are anchored to:
intermediate filaments
26
What are the black arrows pointing to?
spot desmosomes in LM "ladder-like" appearance
27
What is this an image of?
spot desmosomes
28
What to types of junctions anchor the basal surface of a cell?
1. hemidesmosomes 2. focal adhesions
29
Integrins:
* 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
Structure of integrins:
* two subunits (alpha and beta)
31
Integrins interact with what intracellular (cytoplasmic) proteins?
* in focal adhesions = actin * in hemidesmosomes = intermediate filaments
32
Integrins interact with extracellular matrix proteins via:
* an RGD peptide sequence that binds to fibronectin and laminin. * RGD = * arginine * glycine * aspartic acid
33
What is this an image of?
* hemidesmosomes * look like ½ a spot desmosome
34
What protein mediates the interaction of cells and the basement membrane via hemidesmosomes?
* integrin α6β4 * hemidesmosomes are linked to intermediate filaments on the cytoplasmic side
35
Hemidesmosome adhesion protein, plaque protein, and cytoskeletal protein:
* adhesion: integrin α6β4 * plaque: plectin, BPAG 1 * cytoskeletal: intermediate filaments
36
Spot desmosome adhesion protein, plaque protein, and cytoskeletal protein:
* adhesion: cadherins (desmocollin, desmoglein) * plaque: desmoplakin, plakoglobin, plakophilin * cytoskeletal: intermediate filaments
37
Focal adhesions adhesion protein, plaque protein, and cytoskeletal protein:
* adhesion: integrins * plaque: vinculin, talin * cytoskeletal: actin
38
Belt desmosomes adhesion protein, plaque protein, and cytoskeletal protein:
* adhesion: cadherins * cytoskeletal: actin
39
The two cell-cell anchoring junctions:
* belt desmosomes * spot desmosomes
40
The two cell-matrix anchoring junctions:
* hemidesmosomes * focal adhesions
41
Focal adhesions are not visible under conventional EM, but can be visualized using:
immuno-EM
42
Function of focal adhesions:
* important for cell signaling and cell migration * need functioning focal adhesions to have functional hemidesmosomes
43
Gap junctions mainly serve to:
coordinate cellular responses
44
Gap junctions are formed by:
* connexon channels, which allow small molecules like Ca2+ and cAMP to pass from cell to cell.
45
Connexon channel structure:
* formed by six connexin proteins * connexons on cells interact with each other to form a hydrophilic channel between the two cells
46
Connexon permeability is regulated by:
* multiple factors, including: * pH * voltage * calcium
47
What is this an image of?
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
What is this an image of?
clustering of connexons in a gap junction (freeze-fracture EM)
49
What two cell junctions have large extracellular domains?
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
What type of junction is this?
gap junction
51
What type of junction is this?
tight junction
52
What type of junction is this?
belt desmosome
53
What type of junction is this?
spot desmosome
54
Claudin 16 mutation:
* tight junction mutation * autosomal-recessive renal disorder: * hypomagnesemia * hypercalciuria * nephrocalcinosis
55
P-cadherin mutation:
* belt desmosome mutation * early hair loss * progressive degeneration of the central retina
56
Defects in what types of junctions will cause blistering diseases?
* hemidesmosomes * spot desmosomes **DUE TO AN AUTOIMMUNE DISEASE**
57
Pemphigus:
* autoimmune disease with antibodies against desmoglein 1 * defect in spot desmosomes * chronic blistering
58
Pemphigoid:
* autoimmune disease with antibodies against BPAG 1 and 2 * defect in hemidesmosomes * chronic blistering
59
Spot desmosome defects will cause splitting (blisters) where?
* within the epidermal cell layers * due to pemphigus * autoimmune to desmoglein 1
60
Hemidesmosome defects will cause splitting (blisters) where?
* between the epidermis and the underlying basement membrane * due to pemphigoid * autoimmune to BPAG 1 and 2
61
Non-Junctional Adhesion Mechanisms are usually found where?
* during cell locomotion * dynamic cell-cell and cell-matrix adhesions are needed for locomotion
62
Leukocyte extravasation is:
* movement of white blood cells from the capillaries to the tissues surrounding them
63
What adhesion proteins are needed during leukocyte extravasation during the inflammatory response?
* Selectins * Immunoglobulin superfamily (IgCAMs)
64
Selectins:
* transmembrane proteins. * carbohydrate recognition domain that binds oligosaccharides. * **REQUIRE CALCIUM.** * Expressed on the surface of lymphocytes, endothelial cells and platelets.
65
Immunoglobulin superfamily cell adhesion molecules (IgCAMs):
* present on endothelial cells * have Ig-like domains on the extracellular side. * **DO NOT REQUIRE CALCIUM.** * ICAM and VCAM important for homing process.
66
ICAM and VCAM:
* two IgCAMs * present on endothelial cell surfaces * important role in the homing process of leukocytes
67
Full Leukocyte extravasation process:
**_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
The two phases of the leukocyte extravasation process:
* selectin phase * selectin slows down leukocyte * integrin phase * integrins arrest leukocyte

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

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