Cell Adhesion

Question 1

Why do cells stick together?

Answer 1

Important during embryonic development

Question 2

How do cells stick together?

Answer 2

Through adherens junctions and desmosomes

Question 3

What are classical cadherins?

Answer 3

Named after main tissues in which they were discovered

eg- N-casherin ; nerve cells

Question 4

How many casherin proteins in humans?

Answer 4

Over 180

Question 5

Describe the homophilic (like to like) interactions;

Answer 5

Cadherins of one type bind to the same cadherins on adjacent cells

Question 6

What do cadherins require?

Answer 6

Cytoplasmic interactions for strong adhesion and skeletal attachment

Question 7

What are adhering junctions compromised of?

Answer 7

A) p120-catenin

B) B-catenin

C) a-catenin

Question 8

What does the extracellular part of each casherin polypeptide consist of?

Answer 8

Compact domains called casherin repeats, joined by flexible hinge regions

Question 9

When calcium binds near the hinge, what does this cause?

Answer 9

Preventing it from flexing, in the absence of Ca2+ the molecule becomes floppy and adhesion fails

Question 10

Describe casherin interactions;

Answer 10

Weak, low affinity

Clustering of many cadherin

Question 11

Where does binding of cadherins occur?

Answer 11

At the N-terminal tips of the cadherin molecules

The knob of one casherin inserts into a binding pocket in the other

Question 12

What is the protein E-cadherin encoded by?

Answer 12

CDH1 gene

Question 13

What does the transcription factors (snail 1&2) switch off/repress?

Answer 13

The expression of E-casherin from the CDH1 gene

Question 14

How do cancer cells spread?

Answer 14

• downregulation of epithelial adhesion molecules such as E-casherin
• upregulation of mesenchymal cadherins such as N-cadherin

(This process is epithelial mesenchymal transition (EMT)

Question 15

What are snail and ZEB?

Answer 15

Transcription factors induced by a protein called transforming growth factor beta (TCFb)

Question 16

Where are the desmosome found?

Answer 16

Predominant in tissues that experience mechanical stress

Found mainly in skin, epidermis

/ the heart, intestine, gallbladder

Question 17

What are 2 other mediators of cell adhesion?

Answer 17

• selectins

•immunoglobulin superfamily

Question 18

What are glycoproteins?

Answer 18

Proteins decorated with carbohydrates/oligosaccharides. typically short oligosaccharides chains and 1-60% carbohydrate weight

Question 19

What do selectins on the endothelium in blood vessels bind to?

Answer 19

Cell surface oligosaccharides on white blood cells eg neutrophils

Facilitate weak interaction of WBCs with endothelium

Question 20

Describe heterophilic interactions;

Answer 20

• selectins bind to oligosaccharides on glycoproteins and glycolipids

• contrast cadherin- cadherin interactions

Question 21

What do selectin dependent interactions allow?

Answer 21

Loose attachment of WBCs to endothelium

Question 22

What cells are P-selection protein expressed on?

Answer 22

Endothelial cells

Question 23

What is expressed on neutrophils?

Answer 23

P-selectin glycoprotein ligand

Question 24

Neutrophils bind to the endothelial cells, this is mediated by…

Answer 24

P selectin and PSGL

this binding is weak, allowing neutrophils to roll along endothelium

Question 25

What are ICAMS and VCAMs?

Answer 25

ICAMs- intracellular adhesion molecules

IVAMs- vascular cell adhesion molecules

Question 26

What does ICAM do?

Answer 26

On endothelial cells to bind transmembrane proteins known as integrins

Question 27

What is LFA-1?

Answer 27

Lymphocyte function associated antigen-1

Question 28

What do ICAM and VCAM interact with?

Answer 28

Integrins on neurophils

Strengthens the interaction of selectins with P-selectin glycoprotein ligand-1 on neutrophils

Question 29

What does the extracellular matrix contain?

Answer 29

Basal lamina (basement membrane) + connective tissue

Question 30

Describe the basal lamina;

Answer 30

Tough

Flexible thin layer of matrix molecules

Question 31

What does the basal lamina consist mainly of?

Answer 31

Glycoproteins - laminin, collagen IV, nidogen

Proteoglycan- perlecan, aka basement membrane

Question 32

What does basal lamina interact with?

Answer 32

Cells via binding of laminin to integrins

Question 33

Describe the structure of the laminin;

Answer 33

3 intertwined chains with multiple domains for binding other molecules

Question 34

How are cells attached to the basal lamina?

Answer 34

Cells are connected to the basal lamina via binding of laminins to integrins

Question 35

What are integrins?

Answer 35

Heterodimers composed of two transmembrane glycoproteins

Large N-terminal extracellular domains

Short intracellular C-terminal domains

Question 36

What is the job of anchor proteins?

Answer 36

Strengthen the linkage

Question 37

What are the two types of mechanisms of integrin activation?

Answer 37

1) outside-in activation

2) inside-out activation

Question 38

Describe outside-in activation;

Answer 38

Ligand binding to the extracellular domain- leads to exposure of the talin binding site in the intracellular domain of the b-chain

Talin binds, promoting association of actin filaments with intracellular end of integrin

Question 39

Describe inside-out activation;

Answer 39

Talin binds to the b-chain displacing the a subunit

The separation of the intracellular subunits drive the extracellular portion of the integrin into its extended active conformation

Question 40

What is fibronectin?

Answer 40

Dimer of polypeptide chains joined by disulfide bonds