Cell movement Flashcards

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1
Q

What are the principles of actin based cell motility?

A
  • Actin polymerisation can drive movement
  • The actin cytoskeleton is highly dynamic
  • Actin-binding proteins control actin dynamic
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2
Q

What are the minimum requirements for actin based motility?

A
  • Nucleation of new actin filaments
  • Capping of older filaments
  • Recycling of monomers from old filaments - depolymerising and re-polymerising
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3
Q

What are nucleation proteins?

A

Proteins that enhance polymerisation

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4
Q

What are capping proteins?

A

Bind to filaments further back in the cytoskeleton to prevent polymerisation

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5
Q

What are recycling proteins?

A

Recycle actin filaments as they are finite

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6
Q

How are new actin filaments nucleated?

A

Formation of dimers and trimers is energetically unfavourable

However, once formed the trimer rapidly elongates into filaments

Several ABPs can nucleate from the fast growing end of actin filaments

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7
Q

What is the Arp2/3 complex?

A

7 protein complex containing 2 actin-related proteins

Can form a trimer allowing polymerization of new filaments

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8
Q

Where is the Arp2/3 complex localised?

A

Localises to the leading edge of the cell

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9
Q

What does the Arp2/3 complex do?

A

Nucleates new filaments on existing ones to elongate them

Binds on the side of filaments and nucleates new filaments off at a 70 degree angle (branching)

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10
Q

What does the Arp2/3 complex allow for?

A

Allows for directed polymerisation when and where it is needed in a cell

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11
Q

What are the different types of capping proteins?

A
  • Capping protein- dimer of a/b subunits. Found in muscle and non-muscle
  • Gelsolin – an actin binding protein that severs actin filaments and binds to the plus ends
  • gCap39 - Non-muscle capping protein. Similar to gelsolin but does not sever.
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12
Q

Why are capping proteins needed in cells?

A
  • Allows the cells to switch on or off polymerisation
  • Restricts polymerisation to the new filament barbed ends
  • Prevents disassembly
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13
Q

How do capping proteins act as on/off switches?

A

When bound, capping proteins prevent polymerisation

Upon removal of capping proteins, this allows polymerisation of filaments and hence enables cells to move/activating them

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14
Q

What are the recycling proteins?

A
  • ADF/Cofilin

* Profilin

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15
Q

How does ADF/Cofilin recycle actin monomers?

A
  • Binds to actin monomers in the ADP form
  • Binds to actin filaments and destabilises them
  • Appears to be required for actin assembly
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16
Q

How does Profilin recycle actin monomers?

A
  • Profilin binds to actin monomers
  • Profilin binds better to ATP-actin than ADP-actin
  • Profilin can promote the exchange of ADP for ATP
  • Profilin-ATP-actin can add to the barbed ends of filaments
17
Q

How do ADF/Cofinin and Profilin work to promote actin recycling?

A

Cofilin promotes disassembly of ADP actin monomer
Profilin competes with cofilin for binding to ADP actin monomers
Profilin promotes the exchange of ADP for ATP in the cytoplasm
ATP-actin + Profilin assembles on filament

18
Q

What are filopodia?

A

Actin polymerisation driven
Long parallel bundles of filaments
Often accompanied by lamellipodia
Used in sensing the environment - Neurone path finding

19
Q

What are lamellipodia?

A

Actin polymerisation driven
Actin filaments are mainly branched
Formed by nucleation of new filaments and prevention of capping/removal of caps
Used in protrusion
lamellipodia pushes the cell forwards in sheets

20
Q

What are stress fibres?

A

Bundles of actin and myosin

21
Q

What is the process of cell motility?

A

Protrusion
Translocation
Detachment

22
Q

What happens during protrusion?

A

Actin polymerisation
membrane insertion/protrusion
filopodia send chemo signals in a direction to start cell movement
lamellipodia start to spread as the broad sheets elongate

23
Q

What happens during translocation?

A

Formation of new adhesions via integrins
Actin-myosin contractility of stress fibres
traction generated by adhesion
net force is moved backwards which pushes cellular components forwards

24
Q

What happens during detachment?

A

Actin-myosin contractility
Traction generated by adhesion (integrins)
Proteases degrade contacts
Force in cell is generated and so cell moves when back contacts are released

25
Q

How do capping proteins act as restrictors?

A

Uncapped filaments drive polymerisation and therefore cell movement at the lamellipodia

Capped filaments regulate the direction of travel

Uncapping capped filaments changes the direction of travel