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

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
GAPs remove
Phosphate from GTP to put GTPase in inactive state
26
3 Rho family GTPases organise actin
Rho, Rac and Cdc42 | All have different effects on actin organisation
27
Rho induces
Stress fibre formation
28
Rac induces
Lamellipodium formation
29
Cdc42 induces
Filopodium formation
30
Rho family GTPases are activated at specific
Locations
31
Rho family GTPases are activated at
Membranes
32
Protein function is controlled by
Localisation
33
RhoGTPases are controlled by (3)
1. Phosphorylation 2. Localisation 3. Modification by lipids
34
RhoGTPases can be post translationally modified so they can be attached to
Lipid moieties
35
Types of lipid modification (3)
Farnesylation Geranygeranylation Palmitoylation
36
Lipid modification in conjunction with
Sequences at the C terminus of the protein enable the GTPase to bind to membranes
37
If the GTPase is in the right place
Extracellular signalling can phosphorylate the bound GDP and activate the GTPase
38
RhoGTPases demonstrate control by
Localisation
39
RhoGTPases are integrated into lipid bilayers by
Binding to lipids
40
Nocodozole
Disintegrates the MT cytoskeleton
41
Taxol
Stabilises the MT cytoskeleton
42
What organises the active zone of RhoGTPases in wound healing?
Microtubules
43
How many actin binding proteins (ABPs) modify actin organisation and dynamics?
300
44
Some bacteria hijack
The host cell actin cytoskeleton
45
'Rocketing' is
The movement of the bacterium, polymerising host cell actin to move around
46
Rocketing motility uses (4)
1. Actin 2. Arp2/3 complex (protein) 3. Capping protein 4. ADF/cofilin (protein)
47
Rocketing motility does not require
a motor | Myosin
48
Arp2/3 is an
Actin nucleator
49
ADF/cofilin is an
Actin severing and disassembly factor
50
At a certain level, actin is able to polymerise
Spontaneously | from G to F
51
What is the critical concentration of actin
The level at which actin polymerises spontaneously
52
Actin only assembles when it is bound to
ATP
53
Thymosins
Control polymerisation of actin within the cell
54
What is the rate limiting step in actin filament formation?
Nucleation
55
Why is nucleation the rate limiting step in actin formation?
Because short oligomers are unstable and easily disassemble
56
Arp2/3 mimics the structure of
An actin dimer
57
Arp2/3 is able to polymerise actin after
Activation with an activating factor
58
Arp2/3 nucleates actin from the
Minus end
59
The first stable actin structure is
An actin trimer
60
Formins also interact with
RhoGTPases
61
What complex can nucleate branched filaments?
Arp2/3
62
Where are branched filaments found?
Lamellipodium
63
Arp2/3 binds to preexisting
Actin filaments
64
The distance between branched actin filaments is
70 degrees
65
Why is the 70 degree branching angle of actin important?
1. Angle allows more room for actin polymerisation | 2. Angle creates the strongest possible meshwork for pushing the plasma membrane forward
66
Why are capping proteins needed in actin polymerisation? 9£)
1. Stops the filament from getting too long 2. Long filaments are prone to buckling 3. Stops unproductive branches
67
Actin polymerisation uses between
1-10% of the ATP in the cell
68
What stays the same width as the cell migrates?
The lamellipodium
69
What protein allows the cell to stay the same width as it migrates?
ADF/cofilin
70
ADF/cofilin is only active at
The rear of the lamellipodium
71
Keratocyte
Fibroblast
72
Fibroblast
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
Fibroblasts are the most common cells of
Connective tissue in animals
74
What is rate limiting at the leading edge
Actin monomer supply
75
Why is cofilin active at the rear of the lamellipodium?
Needs to supply the leading edge with recycled actin monomer
76
Profilin
Catalyses the regeneration of ATP actin from ADP actin
77
Cofilin only disassembles actin when it is
ADP bound
78
Which 3 proteins work together to form the branched actin network?
Cofilin Arp2/3 Capping protein
79
The dendritic nucleation paradigm
The name for the formation of the branching actin cytoskeleton
80
What do focal adhesions do?
Connect the ESM to the actin cytoskeleton