Lecture 24 - Focal adhesions

Question 1

Active vs inactive adhesion proteins

Answer 1

Active = open -> stretched
Inactive = closed -> folded

Question 2

The ECM

Answer 2

the non-cellular component present within all tissues and organs
- provides essential physical scaffolding for the cell
- biomechanical cues

Question 3

What protein connects the ECM to the cytoplasm?

Answer 3

integrins

Question 4

Conformations of integrin

Answer 4

2
- folds in on itself => hides binding sites
- stretched by pulling ECM out or by talin binding => exposes binding sites

Question 5

What are focal adhesions?

Answer 5

large macromolecular assemblies that form mechanical links between intracellular actin bundles and the ECM

Question 6

Integrins are transmembrane proteins, what do the intracellular and extracellular portions bind to?

Answer 6

intracellular: integrin tail binds to a complex of adaptor proteins that link the actin cytoskeleton (talin and vinculin)
extracellular: binds to ECM proteins like fibronectin or collagen

Question 7

Where can integrins be activated from?

Answer 7

inside or outside of cell
- binding to an ECM substrate
- binding to talin on the inside

Question 8

Integrins cluster to form _____ ______

Answer 8

strong adhesions
- focal adhesions are reinforced over time
- more integrins = stronger adhesion

Question 9

Cell-matrix adhesions respond to _____ _____. What are the main compinents?

Answer 9

mechanical stress; talin and vinculin

Question 10

Talin

Answer 10

• a dimer that binds integrin and actin
• has active and inactive conformations

Question 11

How does talin buffer forces?

Answer 11

through the folding and unfolding of its various rod domains

Question 12

What conformation of talin binds vinculin? Why?

Answer 12

the stretched conformation; talin stretched when the adhesion is not strong enough => binding to vinculin reinforces/strengthens the adhesion

Question 13

What does vinculin do?

Answer 13

it stabilizes talin and integrin at the focal adhesion sites
- vinculin opens up and aids integrin clustering for FA growth
- can bind talin to more actin or binds talin to integrin
- open and closed conformations

Question 14

Focal adhesion kinase

Answer 14

• recruited by talin to FA site
• phosphorylates other proteins at FA site => tells cell where FA is

Question 15

Integrins recruit _______ _______ proteins

Answer 15

intracellular signalling

Question 16

Focal adhesions vs myotendinous junctions

Answer 16

focal adhesions:
- short lived and dynamic
- between migrating cells and ECM

myotendinous junctions:
- muscle attachment sites
- between muscles and tendons
- strong and permanent

Question 17

What happens to myotendinous junctions with no integrin (or other components of the junction)?

Answer 17

the muscles round up
- mechanical tension of junctions is required for muscle shape