10. Cell Motility Flashcards
What is the function of focal adhesions in cell motility?
Act as “hooks” for cells onto surfaces so that they can move forwards in a collective manner
How are focal adhesions formed?
Integrin dimer receptors act as hooks, which attach cytoskeletal components via docking sites in their short cytoplasmic domains
Which cytoskeletal component is used in focal adhesions?
Filamentous actin = like “muscles of cell”
Recall the 3 main peripheral actin structures involved in motility
Lamellipodia
Filopodium
Stress fibres
Describe the structure and function of lamellipodia
Structure: stretchy membrane
Function: expands and contracts to move cell forwards
Describe the structure and function of folipodia
Structure: Finger-like protrusions
Function: sensory = environmental exploratory
Recall the actin arrangement in lamellipodia
Mesh/net-like
Recall the actin arrangement in filopodia
Parallel filaments
Recall the actin arrangement in stress fibres
Anti-parallel (for contraction)
Distinguish G-actin and F-actin
G-actin = monomer F-actin = polymer
Recall the 6 actin-driven processes that need to be controlled
- Remodelling
- Elongation
- Capping
- Severing
- Cross-linking/ bundling
- Branching
Distinguish hapoptatic and chemotactic movement
Hapoptatic = aimless non-directional cell movement Chemotactic = purposeful, polar movement
Which family of proteins are involved in regulation of actin remodelling
Arp
What is the limiting step in actin remodelling reactions
Trimerisation of monomer before it can polymerise
Summarise the control of actin filament elongation
- Promoted by prolifin which binds to G-actin to transport it onto the end of new filaments
- Inhibited by thymosin, which competes with prolifin for actin-binding
Give examples of 2 proteins that bind to the positive end of actin
CapZ
Severin
Give examples of 2 proteins that bind to the negative end of actin
Tropomodulin
Arp
What is the function of severing actin filaments?
Allows growth/ shrinking of filaments to be sped up
Recall the 3 possible fates of severed actin filaments
- Barbed ends capped
- Annealed
- Added to a new strand
Recall 2 proteins involved in control of actin cross-linking and the resulting actin structure
- Alpha-actinin –> cross linking of parallel strands = like a ladder
2, Filamin –> V-shaped actin filament
Which protein family is involved in controlling actin branching?
Arp complex
Recall the family of proteins involved in signalling the development of each different actin structure in locomotion, and which individual protein drives development of each structure
Rho (Subfamily of Ras)
Lamellipodia = Rac
Filopodia = CDC42
Stress fibres = Rho
Summarise the process of de-differentiation that leads to production of a benign tumour
- Disassembly of cell-cell contacts
2. Loss of polarity
Summarise the processes that lead to progression of a benign tumour to a malignancy
Invasion of BM
Increased motility
Cleavage of ECM proteins
Summarise the process of metastasis
• Metastatic cells become mobile mesenchyme-type cells + enter bloodstream. When they reach new organ = lose their mesenchymal characteristics to form new tumour
What are the 2 broad methods of cell migration? Give 2 examples of mechanisms for each of these
- Single-cell (ameboid movement, mesenchymal)
2. Collective movement (clusters, multicellular strands)
Give an example of a cancer type that shows a preference for amyboid movement
Leukaemia
Lymphoma
Give an example of a cancer type that shows a preference for collective multicellular strand movement
Glioblastoma
What genetic change is often seen in tumours that have lost contact-inhibition?
Upregulation of cytoskeletal regulator and motility machinery genes
