L23 - Cell Motility Flashcards

1
Q

What is the ECM made up from

A

Many components including firbronectin, laminin, collagen and elastin

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2
Q

Is fibronectin membrane bound?

A

No is a secreted molecules

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3
Q

How many domains does fibronectin contain - what is the function of these

A

Many domains, one domain binds heparin

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4
Q

Describe the structure of laminin

A

Trimer

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5
Q

What does laminin interact with at its Cā€™ terminal end

A

Integrins, dystroglycans, perelecans

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6
Q

Describe what may increase integrin binding to the ECM

A

Intracellular signsls

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7
Q

Integrins forms

A

Heterodimers

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8
Q

Each monomer of the integrin heterodimer contains

A

One single transmembrane domain

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9
Q

What sort of bonds are found in the a subunit of integrin - where do these bonds form

A

Disulphide bonds - cytenine rich doamins

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10
Q

The N terminal of integrins is capable of binding

A

Divalent cations

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11
Q

What are the two itnegrin subints

A

a and B

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12
Q

What does integrin connect to inside of the cell - what mediates this

A

Binds actin filaments which is mediated by tali and vinculin

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13
Q

How many a integrin types

A

18

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14
Q

How many b integrin subtypes

A

8

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15
Q

How many total variatns can the different a and b integrin subunits form

A

24 variants

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16
Q

Describe the structure of inactive integrin

A

EC domain is folded up into its inactive state

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17
Q

When the EC domain of integrin bind s to the ECM describe what happens

A

Induction of confirmational changes which causes activation of the IC domain this is outside in activation

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18
Q

Desribe inside out activation of integrins

A

Activation of the IC domain through IC signalling - interaction with talin causing the activation of the EC domain

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19
Q

What is FAK

A

Focal adhesion kinase

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20
Q

Describe how FAK is activated

A

Intregrin binding to the ECM causes phosphorylation and activation of FAK

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21
Q

Describe the FAK pathway

A

Fibroncectin interacts with integrin - activates FAK - Phosphorylation of tyrosines in that region of focal adhesion - polymerisation of actin fibres

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22
Q

What is Fak involved in

A

The recycling of focal adhesions to enable migration - acts a timer for the adhesion

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23
Q

If certain cell types are not adhered to their substrate describe what happens

A

Cell death follows this is mediated throguh focal adhesion kinases

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24
Q

What is the name of the process of cell death which occurs when attachement to the substrate is lost

A

Anoikis

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25
Q

Mammalian cell motility is mostly based on which molecule

A

Actin based

26
Q

What are excluded from the region where actin filaments push through

A

Microtubules and intermediate filaments

27
Q

Ruffling is dependent on what and allows the sensing of

A

Actin and allows the sensing of guidance cues

28
Q

Myosin II assists in the

A

Retraction of the tail

29
Q

The lamellipodium extends in direction

A

Of migration

30
Q

What does the cortex aid

A

Membrane tension

31
Q

What is added at the leading edge

A

Actin fibres

32
Q

Tension is transmitted via the

A

Cortex

33
Q

How is the cell highly polarised during migration

A

Different things are happening at either of the ends

34
Q

What is the action of cytochalasin B

A

Lands on + ends of the actin and prevents any further elongation

35
Q

Once actin is capped what begins to be seen

A

Actin filaments begin to depolymerise

36
Q

What activateds the ARP complex

A

Rax kinase

37
Q

What is the function of the ARP complex

A

Nucleation of actin monomrs to form filaments

38
Q

How does ARP2/3 aid in actin nucelation

A

Both resemble actin so aid nucleation in this way

39
Q

Actin branches from at what angle

A

70

40
Q

Describe how branch formation aids in the movement of the cell

A

Branches are forming to push the leading edge forward

41
Q

What happens to actin at the - end? What must then happen to it

A

Actin depolymerises - must be transported back to the leading edge so that they can be assemble

42
Q

When the rear edge is moving forward - what must happen to interactions

A

They are broken

43
Q

Focal contacts are

A

Turned over

44
Q

What have roles in the maturation of focal adhesions

A

Actin binding proteins, small G-proteins, myosins

45
Q

Low density adhestions are

A

Very sparse

46
Q

Low density adhesions require

A

Rac1 and cdc42

47
Q

High density adhesions require

A

RhoA and actin-myosin interaction

48
Q

Describe the mobility of low density adhesions

A

Immobile

49
Q

Descirbe the mobility of high density adhesions

A

Slide in the membrane

50
Q

Example of a soluble molecules as a signal for motility

A

Netrins

51
Q

How can fibronectin be a signal for migrating cells

A

Specific forms of fibronecctin can be laid down which other cells are then able to follow

52
Q

Describe the affect of using antibodies to fibronectin

A

Inhibits migration as interaction with fibronectin is no longer possible

53
Q

Which motif does fibronectin recongise and bind to

A

Arg Gly, Asp

54
Q

What is the Arg, Gly, Asp motif also known as

A

RGD

55
Q

What is the effect of injection of an RGD motif

A

Inhibits migration since fibronectin binding sites are swamped out and binding no longer possible

56
Q

Exocytosis occurs where

A

At the leading end

57
Q

Where does endocytosis occur

A

Arround the cell

58
Q

Overall is there a net membrane addition or removal

A

Addition

59
Q

If membrane is fixed by focal contacts and membrane cycling is occuring what is the effect of this on the cell

A

Cell is able to move forward

60
Q

What are the roles (4) of endocytosis in motility

A

Shaping chemotactic gradients: Confining signalling: Modulation of adhesion contacts and ECM: Polarisation of endocytosis

61
Q

How is adhesion removed

A

Receptor pulled out of the membrane