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MCDone > Regulation of Cell Motility > Flashcards

Regulation of Cell Motility Flashcards

1
Q

What are the changes that occur in the cells that occur during tumour progression?

A

Genetic alterations lead to hyperproliferation, disassembly of cell-cell contacts, loss of polarity, increased motility and cleavage of ECM proteins

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2
Q

What are the different types of tumour cell migration?

A 
Single cell migration (ameboid) 
Mesenchymal single cells  
Mesenchymal chains  
Clusters/cohorts 
Multicellular strands/sheets
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3
Q

What physiological phenomena does tumour migration mimic?

A

Morphogenesis e.g. angiogenesis

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4
Q

What did a comparison of the expression profile of invasive cells vs primary tumours show to be upregulated in invasive cells?

A

Cytoskeleton regulation

Motility machinery

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5
Q

What makes normal migrating cells stop moving?

A

Contact inhibition of locomotion

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6
Q

How are tumour cells different in this aspect?

A

They lose contact inhibition of locomotion so they can multilayer

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7
Q

What is another term for ECM proteins?

A

Substratum

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8
Q

What are filopodia?

A

Finger-like protrusions that are rich in actin filaments

They sense the local environment

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9
Q

What are lamellipodia?

A

Sheet-like protrusions that are rich in actin filaments

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10
Q

What are the four main stages of cell movement?

A

Extension
Adhesion
Translocation
De-adhesion

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11
Q

What are the attachments between the cell and the surface that it is moving along called?

A

Focal adhesions

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12
Q

What are the monomers of actin filaments?

A

G-actin

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13
Q

Describe the polarity of acting filaments.

A

They have a plus end and a minus end

The monomers preferentially get added on at the plus end

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14
Q

What protein complex is important in initiating polymerisation?

A

Arp2/3

This forms a trimer with actin and is good at initiating polymerisation

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15
Q

What is the limiting step in actin dynamics?

A

Formation of Arp2/3-actin trimers to initiate polymerisation

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16
Q

State two proteins that bind to free G-actin and describe how they affect elongation.

A

Promote elongation – profilin (these deliver the G-actin to the growing filament)
Sequesters G-actin addition- thymosin

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17
Q

What regulates addition of g actin to polymer

A

Balance between elongation using profilin and sequestering via thymosin

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18
Q

Name some + end capping proteins.

A

CapZ
Gelsolin
Fragmin/severin

19
Q

Name some – end capping proteins.

A

Tropomodulin

Arp2/3

20
Q

Name some severing proteins.

A

Gelsolin ADF
Framin/severin
Cofilin

21
Q

What are the features of the actin filaments in severed populations?

A

Actin filaments can grow and shrink more rapidly

Better if they are unsevered

22
Q

What can happen to single filaments of actin to improve their structural integrity?

A

They can be bundled or cross-linked

23
Q

Name some proteins involved in actin linking

A 
Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin
24
Q

Which protein allows branching of the actin filaments?

A

Arp2/3

25
Q

At what angle do they branch?

A

70 degree

26
Q

Summarise the actions of Arp2/3.

A

They initiate nucleation
They cap filaments
They cause branching

27
Q

Describe what causes the gel-sol transition.

A

The actin filaments can be severed to make the cell more fluid

28
Q

Describe the actin processes that take place during the protusion of lamellipodia.

A

There is polymerisation, disassembly, branching and capping
There is net filament assembly at the leading edge

29
Q

Describe the actin processes that take place during the formation of filopodia finger protrusion

A

Actin polymerisation
Bundling and cross-linking
(NO branching)
As soon as the finger wants to retract it will collapse at the base

30
Q

State four signalling mechanisms that regulate the actin cytoskeleton.

A

Ion flux changes
Phosphoinositide signalling
Kinases/phosphatases
Small GTPases

31
Q

What are the three most important small GTPases in terms of the actin cytoskeleton and what does activation of each cause?

A

Cdc42 – filopodia
Rac – lamellipodia
Rho – stress fibres
NOTE: these are all part of the Rho family

32
Q

Explain how Rac causes actin polymerisation/organisation.

A

Rac binds to and activates WAVE

WAVE then activates Arp2/3, which is important in actin organisation

33
Q

Explain how Cdc42 causes actin polymerisation/organisation.

A

Cdc42 binds to WASP

WASP also activates Arp2/3

34
Q

Which small GTPases are involved in lamellipodia protrusion?

A

Rac

35
Q

Which small GTPases are involved in focal adhesion assembly?

A

Rac and Rho

36
Q

Which small GTPases are involved in contraction?

A

Rho (stress fibres are important for contraction)

38
Q

Important proteins in all types of cell migration

A

Proteases and integrins

39
Q

Important proteins specific to collective cell migration

A

Cadherins and gap junctions

40
Q

What changes does cell undergo before migration

A

Changes shape so normally goes from round to having a leading edge
Cells become polarised in half of direction of movement
Organelles become polarised in that region

41
Q

Name of large filamentous actin polymer

A

F-actin

42
Q

What is important process associated with extension during movement

A

Polymerisation of actin

43
Q

Important process in adhesion during cell movement

A

Gel/sol transition so cell becomes more flexible

44
Q

Important process in translocation in cell movement

A

Contraction of actin to move cell along

45
Q

What happens if growth signal factor turns up in opposite direction to travel

A

Actin is disbanded into g actin and reassembled on other side

Note the power of one of these signals

MCDone (43 decks)

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