Cell adhesion Ii - The social life of cells

Question 1

What are adherens junctions?

Answer 1

Mediate cell-cell adhesion

Anchor actin microfilaments to the membrane

Question 2

What are adherens junctions composed of?

Answer 2

Classical cadherins - E cadherin
Beta catenin or Plakoglobin
Alpha catenin

Question 3

What are the main classical cadherins?

Answer 3

E-cadherin (epithelial)
N-cadherin (neuronal)
P-cadherin (placental)
VE-cadherin (vascularised epithelial)

Question 4

What are classical cadherins?

Answer 4

Single pass transmembrane glycoproteins
ECM consists of 5 cadherin repeat domains
Adhesion is Ca dependent
Cadherins are arranged in parallel in AJs

Question 5

What is the cadherin superfamily?

Answer 5

Classical - Interact with cytoplasmic proteins and are linked to actin microfilaments

Desmosomal - Interact with cytoplasmic proteins and are linked to IFs

+ others

Question 6

What is the role of cadherins in morphogenesis?

Answer 6

Appearance and disappearance of specific cadherins drives morphogenesis
eg. in neurulation

Question 7

What is morphogenesis?

Answer 7

Process by which anatomical structures are generated and organised.

Question 8

What is neurulation?

Answer 8

Formation of the neural tube during embryogenesis at 3-4 weeks old

Question 9

Explain how cadherins drive neurulation?

Answer 9

1. Epithelial cells of ectoderm lose E-cadherin expression and aquire N-cadherin
2. Cadherin change causes cells to segregate and the ectoderm to invaginate and pinch off to form part of the tube
3. Cells that are a part of the neural tube lose N-cadherin and gain expression of Cadherin-7
4. This allows neural crest cells to migrate from the neural tube.
5. Two groups of migrating cells now re-express N-cadherins allowing them to aggregate and form peripheral ganglia

Question 10

What does cadherin allow for neurulation to take place?

Answer 10

Because cadherins are differentially adhesive

Question 11

What is Epithelial-Mesenchymal Transition (EMT)?

Answer 11

The process whereby epithelial cells lose their normal characteristics (adhesive, non-motile) and gain new characteristics (non-adhesive, motile)

Question 12

How can EMT be induced?

Answer 12

Alterations in adhesion between cells

Question 13

How can the loss of E-cadherin expression relate to cancer?

Answer 13

Loss of expression of Ecadherin and reduced cell adhesion can result in an EMT and:
• loss of histological structure
• increased motility
• increased invasiveness

Characteristics of cancer

Question 14

How can the loss of E-cadherin expression promote invasion and metastasis?

Answer 14

• loss of E-cadherin mediated cell-cell adhesion allows invasion of the underlying connective tissue
• tumour cells are then able to enter the bloodstream by crossing the wall of a blood vessel
• these cells exit from the vessel elsewhere in the body and grow at a new site, forming a metastasis

Question 15

What are focal adhesions?

Answer 15

Mediate cell0matrix adhesion

Found in epithelial or non-epithelial cells

Anchor actin microfilaments to the membrane

Question 16

What are focal adhesions composed of?

Answer 16

Integrins - alpha and beta dimers
Structural proteins - Talin
Signalling proteins - Focal adhesion kinase FAK

Question 17

What are integrins?

Answer 17

alpha and beta heterodimeric transmembrane receptors composed of 2 non-covalently linked subunits

18 alpha and 6 beta proteins combine forming 24 different dimers

Question 18

What do almost all integrins link to?

Answer 18

microfilaments

Question 19

What does the a6b6 integrin link to?

Answer 19

IFs in hemidesmosomes

Question 20

What is the inactive and active states of integrins?

Answer 20

Inactive - alpha and beta chains are tightly folded

Active - Chains unfold into an extended confromation

Question 21

How can activation of integrins be triggered?

Answer 21

Outside-in signalling: binding to a ligand (ECM protein)

Inside-out signalling: binding to talin

Question 22

What is Outside-in signalling?

Answer 22

Integrins bind and switch to their active conformations when cells come into contact with ECM proteins

Increases integrin affinity for talin and enables them to recruit it to form to FA complex

FA complex is important for cell migration and cell growth

Question 23

What is Inside-out signalling?

Answer 23

Platelets express aIIb3 integrin (inactive state)

When platelets come into contact with thrombin, Talin is activated and this activates aIIb3 integrin

Increases the affinity of aIIb3 for fibrinogen and leads to the formation of the platelet plug at the site of injury

Question 24

What is Glanzmanns disease?

Answer 24

Mutation in either aII or B3 integrin chains preventing the interaction of platelets with fibrinogen at site of blood clots.

This is characterised by defective clotting and excessive bleeding.