Cell- ECM interaction

Question 1

How do cells secrete their own ECM

Answer 1

They do this by :
synthesising
Organising
degrading

Question 2

What is the the cell - ECM junction

Answer 2

These are the junctions that link the ECM to the cytoskeleton of the cells allowing for :

1) Adhesion
2) Force transmission
3) Signalling
4) Mechanotransduction

Question 3

What is the adhesive protein found in cell - ecm junctions

Answer 3

Intergrins

Question 4

Describe the basic structure of intergrins and its linkages

Answer 4

• Conatins heterodimers:
  Alpha subunit and beta subunit
• Humans have 24 intergrins
• The intergrins bind to the ECM proteins eg) RGD motifs / fibronectin
• They bind to the actin filaments in the cell via
• Vinculin
• Talin
• Tensin

Question 5

Describe the states of the intergrins when active and inactive

Answer 5

Inactive = Bent . ECM has low affinity and tail is together

Active = Extended , high ECM affinity , tail is seperated

Question 6

How does the intergrin bind to the ECM

Answer 6

• The intergrin binds with the ECM proteins eg) Fibronectin

Question 7

How does the intergrin link to the cell

Answer 7

• Intergrin beta tail will bind to talin
• This links the intergrin to the actin filament

Question 8

Describe the mechanotransduction between the cell and ECM

Answer 8

• Intergrin is connected the actin filament via Talin
• Myosin II walks along the actin filament and generates a force.
• This tension will cause the talin/ intergrin complex to stretch
• The stretching exposes cryptic binding sites which will recruit vinculin
• The recruitment of vinculin will results in more linkages of teh adhesion proteins with the cytoskeleton hence strengthening the adhesion

Question 9

Describe the relationship between the stiffness of the ECM and focal adhesion

Answer 9

• When an ECM is stiff this means that the stretching of the adhesion proteins at the joints will be met with resistance hence generating tension.
• This tension will result in more focal adhesions being formed
• When a ECM is soft there will be less tension hence talin will not be stretched. Fewer vinculin generated hence you will find fewer and weaker focal adhesions

Question 10

What is FAK and what is its function

Answer 10

Focal adhesion Kinase

• This is activated when the intergrins cluster together
• This triggers intracellular signalling which regulates

1) Migration
2) Proliferation
3) Adhesion turnover

Question 11

Discuss the importance of ECM Degradation

Answer 11

• The cell needs to be able to degrade its own ECM
• This is important for tissue repair
  matrix turnover
• This is done through MM (matrix metalloproteases)
  Serine proteases