Lecture 9 - Cell migration and adhesion (Actin based) Flashcards

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1
Q

Force generated by actin polymerisation allows

A

Amoebae and metazoan cells to have ‘crawling’ motility

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2
Q

Cells can migrate (2)

A

Individually or as a collective epithelial sheet

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3
Q

The stages of cell migration (4)

A
  1. Cell receives a signal
  2. Actin protrusion
  3. Attachment and traction
  4. Contraction
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4
Q

The actin cortex is

A

gives the cell shape but is not a cell wall, so shape can be changed
underlies the plasma membrane

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5
Q

Actin protrusion is

A

Actin polymerisation at the plus end causes the lamellipodium to protrude
Pushes the plasma membrane forward

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6
Q

Lamellipodium

A

Lamel - latin, sheet
pod - latin, foot
Cytoskeletal actin projection at the leading edge of the cell

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7
Q

Attachment to the extracellular environment allows

A

The cell protrude, stick and retract the tail

Attachment is integral to generating force to move

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8
Q

Actin is

A

A polar filament

Many different types allow cell migration

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9
Q

Filopodia

A

Slender cytoplasmic projections (‘fingers’) that extend beyond the leading edge of lamellipodia in migrating cells
Contain actin filaments cross-linked into bundles by actin-binding proteins, e.g. fascin and fimbrin

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10
Q

Actin structures within the cell (3)

A
  1. Stress fibres (cell cortex)
  2. Filopodia
  3. Dendritic meshwork
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11
Q

Stress fibres have

A

Alternating polarity (as do muscle fibres)

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12
Q

What do filopodia do

A

Sense the environment

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13
Q

Filopodia have

A

Uniform polarity (unidirectional)

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14
Q

Dendritic

A

Branching

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15
Q

Lamellipodium have

A

Graded polarity (criss crossing)

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16
Q

Actin fibres are always

A

Bundled

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17
Q

Rho GTPases are

A

Molecular switches involved in cell signalling

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18
Q

Cdc42

A

Master regulator of cell polarity

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19
Q

Cell signalling: Mechanism for RhoGTPase

A
  1. Inactive GTPase bound to GDP
  2. Signal is recieved
  3. GEFs add GTP to GTPase
  4. Active GTPase promotes signalling
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20
Q

GEFs

A

Guanine nucleotide exchange factors

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21
Q

GAPs

A

GTPase activating proteins

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22
Q

GAPs turn

A

cell signalling off

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23
Q

GEFs turn

A

cell signalling on

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24
Q

GEFs add

A

GTP to GTPase

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25
Q

GAPs remove

A

Phosphate from GTP to put GTPase in inactive state

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26
Q

3 Rho family GTPases organise actin

A

Rho, Rac and Cdc42

All have different effects on actin organisation

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27
Q

Rho induces

A

Stress fibre formation

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28
Q

Rac induces

A

Lamellipodium formation

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29
Q

Cdc42 induces

A

Filopodium formation

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30
Q

Rho family GTPases are activated at specific

A

Locations

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31
Q

Rho family GTPases are activated at

A

Membranes

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32
Q

Protein function is controlled by

A

Localisation

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33
Q

RhoGTPases are controlled by (3)

A
  1. Phosphorylation
  2. Localisation
  3. Modification by lipids
34
Q

RhoGTPases can be post translationally modified so they can be attached to

A

Lipid moieties

35
Q

Types of lipid modification (3)

A

Farnesylation
Geranygeranylation
Palmitoylation

36
Q

Lipid modification in conjunction with

A

Sequences at the C terminus of the protein enable the GTPase to bind to membranes

37
Q

If the GTPase is in the right place

A

Extracellular signalling can phosphorylate the bound GDP and activate the GTPase

38
Q

RhoGTPases demonstrate control by

A

Localisation

39
Q

RhoGTPases are integrated into lipid bilayers by

A

Binding to lipids

40
Q

Nocodozole

A

Disintegrates the MT cytoskeleton

41
Q

Taxol

A

Stabilises the MT cytoskeleton

42
Q

What organises the active zone of RhoGTPases in wound healing?

A

Microtubules

43
Q

How many actin binding proteins (ABPs) modify actin organisation and dynamics?

A

300

44
Q

Some bacteria hijack

A

The host cell actin cytoskeleton

45
Q

‘Rocketing’ is

A

The movement of the bacterium, polymerising host cell actin to move around

46
Q

Rocketing motility uses (4)

A
  1. Actin
  2. Arp2/3 complex (protein)
  3. Capping protein
  4. ADF/cofilin (protein)
47
Q

Rocketing motility does not require

A

a motor

Myosin

48
Q

Arp2/3 is an

A

Actin nucleator

49
Q

ADF/cofilin is an

A

Actin severing and disassembly factor

50
Q

At a certain level, actin is able to polymerise

A

Spontaneously

from G to F

51
Q

What is the critical concentration of actin

A

The level at which actin polymerises spontaneously

52
Q

Actin only assembles when it is bound to

A

ATP

53
Q

Thymosins

A

Control polymerisation of actin within the cell

54
Q

What is the rate limiting step in actin filament formation?

A

Nucleation

55
Q

Why is nucleation the rate limiting step in actin formation?

A

Because short oligomers are unstable and easily disassemble

56
Q

Arp2/3 mimics the structure of

A

An actin dimer

57
Q

Arp2/3 is able to polymerise actin after

A

Activation with an activating factor

58
Q

Arp2/3 nucleates actin from the

A

Minus end

59
Q

The first stable actin structure is

A

An actin trimer

60
Q

Formins also interact with

A

RhoGTPases

61
Q

What complex can nucleate branched filaments?

A

Arp2/3

62
Q

Where are branched filaments found?

A

Lamellipodium

63
Q

Arp2/3 binds to preexisting

A

Actin filaments

64
Q

The distance between branched actin filaments is

A

70 degrees

65
Q

Why is the 70 degree branching angle of actin important?

A
  1. Angle allows more room for actin polymerisation

2. Angle creates the strongest possible meshwork for pushing the plasma membrane forward

66
Q

Why are capping proteins needed in actin polymerisation? 9£)

A
  1. Stops the filament from getting too long
  2. Long filaments are prone to buckling
  3. Stops unproductive branches
67
Q

Actin polymerisation uses between

A

1-10% of the ATP in the cell

68
Q

What stays the same width as the cell migrates?

A

The lamellipodium

69
Q

What protein allows the cell to stay the same width as it migrates?

A

ADF/cofilin

70
Q

ADF/cofilin is only active at

A

The rear of the lamellipodium

71
Q

Keratocyte

A

Fibroblast

72
Q

Fibroblast

A

A cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing

73
Q

Fibroblasts are the most common cells of

A

Connective tissue in animals

74
Q

What is rate limiting at the leading edge

A

Actin monomer supply

75
Q

Why is cofilin active at the rear of the lamellipodium?

A

Needs to supply the leading edge with recycled actin monomer

76
Q

Profilin

A

Catalyses the regeneration of ATP actin from ADP actin

77
Q

Cofilin only disassembles actin when it is

A

ADP bound

78
Q

Which 3 proteins work together to form the branched actin network?

A

Cofilin
Arp2/3
Capping protein

79
Q

The dendritic nucleation paradigm

A

The name for the formation of the branching actin cytoskeleton

80
Q

What do focal adhesions do?

A

Connect the ESM to the actin cytoskeleton