Cell-Matrix Adhesion Flashcards

1
Q

What is fibronectin

A

Large glycoprotein
Helps organise ECM and cell attachment

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2
Q

How is fibronectin structured?

A

Multiple type I-III repair domains in a beads on a string conformation

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3
Q

What is the role of fibronectin molecules in blood clotting?

A

After blood clot forms, fibrin clot forms.
FIbronectin forms bridges between fibrin strands.

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4
Q

What cell adheres to fibronectin in wound healing?

A

fibroblast

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5
Q

Fibroblasts lead to granular tissue formation in wound healing.
What does the granular tissue matrix convert fibroblasts to?
And what is their fucntion?

A

myofibroblasts
Contract which help pull the wound edges closer together

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6
Q

What happens to fibronectin conformation under applied force?

A

FN Type 3 has no disulphide bonds so unfolds under applied force

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7
Q

Why does T3 fibronectin unfold?

A

Allows FN molecules to bind to each other

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8
Q

When a cell (like a fibroblast) starts to move, where does fibronectin get deposited?

A

at the leading edge

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9
Q

What are the areas of a moving cell in which fibronectin is highly concentrated called?

A

focal complexes

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10
Q

What happens to focal complexes when actin filaments attach?

A

Focal complexes become focal adhesions

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11
Q

How does tensile strength cause formation of fibronectin fibrils?

A

Tensile strength causes unfolding of fibronectin to reveal new sites.
Other fibronectins bind to these newly exposed sites.

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12
Q

What is the role of integrins in focal complexes/adhesions?

A

Integrins act as a bridge between fibronectin (ECM compomnent) and the cell

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13
Q

What are integrins?

A

Integrins are a family of transmembrane proteins that function as cell surface receptors.

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14
Q

What is the role of integrin heterodimers in hemidesmosomes?

A

Integrin mediates the attachment of the epithelial cell to the basement membrane.
Integrin binds to laminin on BM.

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15
Q

How do hemidesmosomal integrins aid in mediating attachment of epithelial cell to BM?

A

Creates stable bridge between ECM and epithelial cell.

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16
Q

What does intracellular and extracellular portion of hemidesmosomal integrin bind?

A

Extracellular domain binds laminin.
Intracellular domain binds intermediate filaments cytoskeleton.

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17
Q

Are hemidesmosomes static or dynamic?

A

usually static, but become dynamic when endothelial cells need to move (like to a wound).

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18
Q

How many subunits does integrin have?

A

Two
Alpha and beta
Not covalently attached

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19
Q

what is the structure of intracellular domain of integrin?

A

C terminal tails (on both subunits)

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20
Q

Which ions are important in the specificity of binding of integrins to ECM ligands?

A

calcium and magnesium ions

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21
Q

Do all human integrins bind to actin filaments?

A

23 do, 1 doesn’t

22
Q

What does alpha6beta4 integrin bind to?

A

laminin

23
Q

Where is alpha5beta4 integrin found?

A

hemidesmosomes

24
Q

Which integrin beta subunit has a large intracellular domain?

A

beta4

25
Q

(in hemidesmosomes) Integrin beta4 binds to keratin intermediate filament through which two cytoskeletal adapter proteins?

A

plectin and BPAG1
(both Plakin protein family)

26
Q

What other transmembrane component is alongside integrin in hemidesmosomes?

A

BPAG2
(collagen 17)

27
Q

Which two components make up the outer plaque structure of hemidesmosomes?

A

integrin and collagen 17

28
Q

Which two components make up the inner plaque structure of hemidesmosomes?

A

Plectin and BPAG1

29
Q

What do alpha6beta4 integrin and collagen 17 bind to on the ECM’s basement membrane?

A

Laminin 332

30
Q

Where is laminin 332 found?

A

In the lamina densa in basement membrane

31
Q

What connects the laminin 332 in the lamina densa to the connective tissue in the dermis layer?

A

collagen VII

32
Q

Which integrin is expressed on the surface of T cells?

A

LFA1
(Lymphocyte function-associated antigen 1)

33
Q

What does LFA1 on T cell bind to when it encounters an APC?

A

LFA1 weakly binds to ICAM on APC

34
Q

Under what situation does LFA1 on T cell bind STRONGLY to ICAM on APC?

A

If T cell receptor recognises an antigen on MHC of APC.

35
Q

When do rolling leukocytes encounter Platelet Activating Factor (PAF) ?

A

From endothelial cells when they reach closer to the site of inflammation

36
Q

What does Platelet Activating Factor (PAF) on endothelial cells trigger in leukocytes?

A

Outside-in signalling
activation of LFA1(leukocyte function associated antigen 1) integrin.

37
Q

What does strong LFA1 integrin (on T cell) and ICAM1 (on endothelial cell) lead to during leukocyte recruitment?

A

Leads to extravasation of T cells from blood stream to site of inflammation.

38
Q

Difference in structure between active and inactive integrins ?

A

when inactive they are compact and the cytoplasmic tails are locked together

39
Q

Which type of integrin activation involves Talin?

A

Inside-out signalling

40
Q

How does Talin activate integrin during inside-out signalling?

A

Talin binds to cytoplasmic domains (inactive conformation).
Unhooks the cytoplasmic domain.
Causes unfolding of extracellular domains.

41
Q

What do the C terminal and N terminal of Talin bind to?

A

C terminal: binds integrin
N-terminal: binds actin filaments

42
Q

What actin regulatory protein can bind to Talin (in areas that are hidden when Talin is folded)?

A

vinculin

43
Q

Which integrin is important in the development of blood clots?

A

alpha2beta3 integrin

44
Q

Which integrin does thombrin activate, and which molecules mediate this activation?

A

Integrin alpha2beta3

Mediated by Rap1, RIAM, Talin, kindlin.

45
Q

What happens to platelets as a result of integrin alpha2beta3 activation?

A

the platelets become sticky

46
Q

What type of blood clots are created during wound healing?

A

insoluble blood clots

47
Q

As well as being transmembrane receptors for ECM proteins, integrins are also signalling molecules/environmental sensors.

What type of signals do integrins transduce?

A
  • tissue stiffness
  • matrix composition
  • presence of growth factors
48
Q

Where Focal Adhesion Kinase (FAK) phosphorylated and what does it do?

A

FAK is phosphorylated at focal adhesion sites.

FAK creates docking sites for RhoGTPases like RhoA.

This leads to actin filaments becoming contractile stress fibres.

49
Q

What recruits FAK to focal contacts?

A

Talin

50
Q

What is anchorage dependence?

A

Where cells need to be attached to ECM in order to survive

51
Q

Can cells survive when attached to ECM in only one patch?

A

NO.
Must be distributed in multiple spots.