Cell movement Flashcards
What are the principles of actin based cell motility?
- Actin polymerisation can drive movement
- The actin cytoskeleton is highly dynamic
- Actin-binding proteins control actin dynamic
What are the minimum requirements for actin based motility?
- Nucleation of new actin filaments
- Capping of older filaments
- Recycling of monomers from old filaments - depolymerising and re-polymerising
What are nucleation proteins?
Proteins that enhance polymerisation
What are capping proteins?
Bind to filaments further back in the cytoskeleton to prevent polymerisation
What are recycling proteins?
Recycle actin filaments as they are finite
How are new actin filaments nucleated?
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
What is the Arp2/3 complex?
7 protein complex containing 2 actin-related proteins
Can form a trimer allowing polymerization of new filaments
Where is the Arp2/3 complex localised?
Localises to the leading edge of the cell
What does the Arp2/3 complex do?
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)
What does the Arp2/3 complex allow for?
Allows for directed polymerisation when and where it is needed in a cell
What are the different types of capping proteins?
- 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.
Why are capping proteins needed in cells?
- Allows the cells to switch on or off polymerisation
- Restricts polymerisation to the new filament barbed ends
- Prevents disassembly
How do capping proteins act as on/off switches?
When bound, capping proteins prevent polymerisation
Upon removal of capping proteins, this allows polymerisation of filaments and hence enables cells to move/activating them
What are the recycling proteins?
- ADF/Cofilin
* Profilin
How does ADF/Cofilin recycle actin monomers?
- Binds to actin monomers in the ADP form
- Binds to actin filaments and destabilises them
- Appears to be required for actin assembly
How does Profilin recycle actin monomers?
- 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
How do ADF/Cofinin and Profilin work to promote actin recycling?
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
What are filopodia?
Actin polymerisation driven
Long parallel bundles of filaments
Often accompanied by lamellipodia
Used in sensing the environment - Neurone path finding
What are lamellipodia?
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
What are stress fibres?
Bundles of actin and myosin
What is the process of cell motility?
Protrusion
Translocation
Detachment
What happens during protrusion?
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
What happens during translocation?
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
What happens during detachment?
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
How do capping proteins act as restrictors?
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
