The Actin Cytoskeleton Flashcards
(21 cards)
What are the two main classes of actin nucleating proteins?
Formins (assemble unbranched filaments)
Arp2/3 complex (creates branched filaments).
How does actin nucleation relate to signal transduction?
Actin assembly is regulated by signalling pathways that control nucleating proteins
What is the Arp2/3 complex?
A seven-subunit protein complex found in all eukaryotes, including actin-related proteins (ARPs 2 & 3).
What role does Arp2/3 play in cell movement?
It creates branched actin networks in structures like the leading edge of motile cells.
What activates Arp2/3?
Nucleation Promoting Factors (NPFs) such as WASp, which induces filament branching.
How does Arp2/3 nucleate new branches?
Binds to the side of an existing filament
Activating proteins like WASp trigger actin monomer binding
A new actin filament grows from the branch site
How is WASp activated?
Cdc42, a Ras GTPase family protein, binds the Rho Binding Domain (RBD) of WASp, unlocking its activation.
What happens when WASp is activated?
W domain transfers a G-actin monomer to the Arp2/3 complex
A domain + C domain enhance Arp2/3 binding, initiating branching
What disease results from WASp defects?
Wiskott-Aldrich Syndrome → an X-linked immune deficiency (low IgM and blood platelets).
How does actin contribute to endocytosis?
Endocytosis factors recruit NPFs, activating Arp2/3 for actin branching.
How does actin help leukocytes engulf bacteria?
Opsonization (bacterium is coated with antibodies).
Leukocyte Fc receptor binds the antibody-covered bacterium.
Fc receptor activation triggers Arp2/3-mediated actin filament assembly.
Membrane wraps around bacterium, forming a phagosome.
Lysosomes fuse with the phagosome, releasing enzymes to degrade bacteria.
How does Listeria monocytogenes move inside host cells?
It hijacks the actin polymerization machinery, creating comet tails for propulsion.
What proteins are required for Listeria comet tail formation?
ATP-G-actin
Arp2/3 complex
CapZ (caps filament ends)
Cofilin (enhances depolymerization at (-) end)
How does Listeria propel itself?
ActA protein on Listeria surface activates Arp2/3 → generating branched filaments.
Filaments grow until capped by CapZ → controlling growth direction.
Cofilin recycles actin at the (-) end → sustaining propulsion.
What do formins do?
They nucleate unbranched actin filaments, essential for stress fibers & filopodia formation.
How is actin nucleated by formins?
Formin dimers bind two actin monomers.
Rocking motion promotes monomer addition at the (+) end.
Formins protect filaments from capping proteins, sustaining growth.
What are the two key domains of formins?
FH1 (binds profilin-actin)
FH2 (nucleates filament assembly).
How are formins activated?
Rho GTPase binding exposes FH1 & FH2, promoting actin nucleation.
How does actin organization differ inside cells vs. in a test tube?
Cells contain cross-linking proteins, forming ordered structures like bundles & meshworks.
What do actin cross-linkers do?
They connect filaments into structured networks, regulating cytoskeleton architecture.
What are some types of actin cross-linkers?
1 - Fimbrin → tight bundles in microvilli (aligns filaments with the same polarity).
2 - α-Actinin → loose filament arrangement in stress fibers.
3 - Spectrin → tetrameric, linking actin filaments to plasma membrane.
4 - Filamin → flexible cross-links stabilizing actin networks in motile cells.
5 - Arp2/3 Complex → cross-linking actin at branch points.
