Invasion - regulation of cell migration Flashcards
What cytoskeletal processes occur during locomotion?
Disassembly of actin filaments
Rapid diffusion of subunits
Reassembly of filaments at new site
What are the different types of actin binding proteins?
Nucleating Elongating Sequestering Capping Severing Cross-linking Bundling Branching
How do small G proteins control the actin cytoskeleton?
- Rho subfamily of small GTPases belongs to Ras super-family
- Activated by receptor tyrosine kinase, adhesion receptors and signal transduction pathways
1st activated molecule recruits other molecules needed for polymerisation/organisation
Participate in cell migration
- Extension - Rac - actin polymerisation, branching
- Adhesion - Rac, Rho - focal adhesion assembly
- Translocation - Rho - stress fibres, tension, contraction
- De-adhesion - Rho
Cdc42 - filopodia, polarised motility, actin polymerisation
Why is metastasis significant in cancer development?
Most cancer deaths are caused by metastasis of primary tumour to a secondary site
Harder to treat
What cellular and molecular changes are necessary for metastasis to occur?
- Disassembly, nucleation, branching, severing, capping, bundling, polymerisation during extension in cell motility
- Gel/sol transition and ECM attachment during adhesion
- Contraction during translocation
- Detachment during de-adhesion
- Lamellae protrusion
- Filopodia
What do capping proteins do?
- Regulate elongation process of filaments
- Binds to end of actin filament and prevents monomers joining
- Filaments are very dynamic, joining at front and taking from back
- Results in shortening of filament if only at minus end
- Can cap at plus and minus end
What do cross-linking and bundling proteins do?
Shape fully formed filaments - can bind filaments at different distances
-Bundle filaments together
What do branching proteins do?
Bind actin filaments to one another at 70 degrees, allow nucleation to occur and filaments to elongate at that angle
What happens during the rate-limiting step in the organisation of the cytoskeleton?
Nucleation = rate-limiting step
High energy requirement
Arp = actin relating protein - similar structure to actin
Helps monomers form trimer
Once trimer, polymerisation starts and makes big filament
ARP complex binds to minus end to help actin monomers form trimer, then polymer extends from plus end
What do elongation proteins do?
Bind to monomer and bring it to the filament to add to the minus end - make filament longer
