Co-ordinating Cell Migration Flashcards
(21 cards)
What is the lamellipodium?
A dynamic, branched actin network at the leading edge, created by the Arp2/3 complex.
What are filopodia and how are they formed?
Filopodia are thin, actin-rich projections at the leading edge of motile cells, formed by formin activity.
What is the cortical actin cytoskeleton?
A more stable actin network, providing plasma membrane stability.
What are stress fibers?
Contractile microfilaments that attach to the substratum via focal adhesions, aiding motility.
What are the steps in fibroblast migration?
1️ Membrane Extension → Actin nucleation via Arp2/3, filaments elongate at the (+) end.
2️ Substrate Adhesion → Focal adhesions anchor actin bundles to prevent retraction.
3️ Cell Body Translocation → Cytoskeletal contraction squeezes organelles & nucleus forward.
4️ Rear Detachment & Recycling → Focal adhesions at the tail break, integrins recycle to the front.
How do focal adhesions migrate?
As the cell moves forward, adhesions at the rear are disassembled while new adhesions form at the front.
What are integrins?
Membrane proteins that link the extracellular matrix to the actin cytoskeleton.
What do integrins bind in the extracellular matrix?
Fibronectin
Collagen.
How are integrins recycled?
When focal adhesions reach the back, integrins are internalized via endocytosis and transported forward.
What motor proteins generate contractile forces?
Myosins, which interact with actin filaments to drive movement.
What protein accelerates healing at injury sites?
TGF-β, a cytokine that stimulates immune cell migration.
How does platelet-derived growth factor (PDGF) aid wound healing?
Activates fibroblasts & epithelial cells to repair the wound.
Stimulates small GTPases (Rho family) to reorganize the cytoskeleton for movement.
What role do Cdc42, Rac, and Rho play in migration?
Cdc42 → Filopodia formation & cell polarity.
Rac → Lamellipodia formation via Arp2/3.
Rho → Stress fiber formation & contractile force generation.
How are Rho GTPases activated?
1 Inactive GDP-bound state → Complexed with GDI (Guanine Dissociation Inhibitor) in the cytosol.
2️ Activated by GEF (Guanine Exchange Factor) → GDP replaced with GTP, localizing to the membrane.
3️ Binds effectors at the membrane → Induces actin cytoskeleton rearrangements.
4️ Deactivated by GAP (GTPase Activating Protein) → Hydrolyzes GTP back to GDP, returning Rho to cytosol.
What happens when Rho proteins are mutated?
Constitutively active mutants → Locked in GTP-bound state, causing continuous cytoskeletal activation.
Dominant negative mutants → Predominantly GDP-bound, blocking cytoskeletal reorganization.
How is the wound healing assay performed?
Cells are grown to monolayer in a dish.
A scratch simulates a wound, exposing ECM components.
Cells migrate to close the wound, driven by cytoskeletal reorganization.
GTPase mutants are introduced, assessing their effect on migration.
What happens when Rho GTPases are blocked?
Dominant negative Rac → Poor lamellipodia formation, weak migration.
Dominant negative Cdc42 → Cells lose polarity, unable to move in the correct direction.
Dominant negative Rho → No stress fiber formation, reducing motility.
How do signals coordinate motility?
1️Cdc42 activation → Establishes cell polarity, guiding movement direction.
2️ Cdc42 activates Rac, inducing lamellipodia formation at the leading edge.
3️ Rac promotes Rho activation at the rear, assembling stress fibers.
4️ Rho inhibits Rac, ensuring asymmetry between front & rear movement forces.
What happens if Rho activation is lost?
Loss of contractile stress fibers, impairing movement.
How does Cdc42 contribute to cancer progression?
Stimulates protease release, degrading the extracellular matrix.
Promotes formation of invadopodia, aiding tissue invasion.
Increased Cdc42 levels (not mutations) are commonly seen in tumors.
Why is Cdc42 a target for cancer treatment?
Drugs that reduce Cdc42 activity may slow cancer cell migration and prevent metastasis
