5 – Controlling Actin Flashcards
actin regulators: allow
cells to build diverse & dynamic actin networks
Formins
Grow the filament
-to accelerate rate of actin growth/shut it down
Cofilin
cut the filament
Capping protein
Cap the filament
-stop filament growing
Arp2/3 complex
Make branched networks
-seen in lamellapdoia & leading edge of migrating cells
α-actinin - dimer
Fimbrin
spectrin
filamin
Cross-link/Bundle the filaments
cross-linking process
Crosslinkers have 2 opposite filament binding domain
proteins with 2 actin binding domains & grab onto actin & bind them tgt
3 regulators that work together to drive the forward motion of cells
-branched actin network
-cofilin
-capping protein
Leading edge of moving cell is a
it has a thick…
branched actin net work
-Thick band of actin – constant in thickness
how is thick band of actin constant in thickness
Something in the back depolymerizes it as the leading edge is being polymerized
Lysteria
pathogenic bacterium hijacks actin machinery
lysteria’s comet tail
nucleated by …
force our actin to build dendritic actin network behind them that propels them through your cells
Arp2/3 complex
what is Arp2/3 complex
Actin related protein
Mimics actin nucleus and nucleates daughter filaments at 70˚
Arp2/3 needs to be …
Arp2/3 needs to be activated – to have a conformation change to bring them tgt adjacent to one another
why 70˚
optimal angles for pushing out the plasma membrane
Just enough little space to let actin enter between polymer & membrane
what activated Arp2/3 complex
Activated by WASp (Wiskott-Aldrich Syndrome family proteins)
WH2 domain binds an actin monomer
A domain = Acidic domain induces change in Arp2/3
-binds Arp2/3 complex & induce conformational change that bring Arp2 and 3 together
what happens when Arp 2/3 is activated
WH2 domian will deliver its actin subunit onto Arp2/3 complex
creates a trimer - perfect nucleux & actinfilament can grow
Lysteria Coated with
ActA – protein that mimics WASp
Lamellipodium challenges (2)
-prevent running out of actin
to keep the concentration of actin constant
-Preventing futile polymerization
Ends that are not touching the membrane – not useful to moving
prevent Polymerizing at (-) end – wrong direction
Lamellipodium challenges solutions
-Profilin
Recycles actin
Blocks (-) end polymerization
-ADP fall out while ATP comes in
-ADF/Cofilin
Cuts actin filaments – for constant thickness
Unwinds and break
Together – Cofilin & Profilin
accelerate actin treadmilling
-cofilin depolymerizes
-profilin recharges it
actin is ready to bind to new plus ends of actin filaments
how to prevent wrong filament from polymerizing?
Capping proteins
-Prevents futile polymerization
-Tropomodulin (cap minus end) / Cap Z (cap plus end)
listeria’s Motility = driven by coordinated action of 6 proteins
actin
ActA
Arp2/3
-polymerizes branched actin network
Capping proteins
-Cap Z
Cofilin
-disassembly of actin filaments
Profilin
-recycling of actin
If capping proteins too much =
all actin filaments are capped = no push
-hardly moving
If not enough capping proteins=
too many fialments keeps growing and doesnt push =looks like fish bones
-hardly moving
capping protein in lysteria
capping proteins takes a second to find newly nucleated actin filament and cap it
-this second is important because it gives time for new actin filaments to give a little push before it gets shut down
Leading edge and Listeria comet tails are functionally
equivalent
