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BLG411 Winter 2017Prepared by: Sumaiya IbrahimA modelfor actin filament nucleation by the Arp 2/3 complex. In the absence of an activatingfactor, Arp2 andArp3areheldbytheir accessory proteins in an orientation that prevents them from nucleating a new actin filament. When an activating factor (like N-WASP; indicated by the blue triangle) binds the complex, Arp2 and Arp3 are brought together into a new configuration that resembles the plus end of an actin filament. Actin subunits can then assemble onto this structure, bypassing the rate-limiting step of filament nucleation.Arp2/3 is a more efficient nucleator when bound to pre-existing filamentsFormin proteins form a dimeric complex that can nucleate the formation of a new actin filament and remain associated with the rapidly growing plus end as it elongates. The formin protein maintains its binding to one of the two actin subunits exposed at the plus end as it allows each new subunit to assemble. Only part of the large dimeric formin molecule is shown here. Other regions regulate its activity and link it to particular structures in the cell. Many formins are indirectly connected to the cell PM and aid the insertional polymerization of actin filament directly beneath the membrane surface.7
BLG411 Winter 2017Prepared by: Sumaiya IbrahimFormin-dependant actin filament growth is strongly enhancing by the association of actin monomers with profilin. Some members of the formin protein family have formin whiskersthat contain several binding sites for profilin or the profilin-actin complex. These flexible domains serve as a staging area for addition to the growing plus end of the actin filament when formin is bound.This can enhance the rate of actin filament elongation.Regulation of the Cytoskeleton – Severing, Capping, Depolymerization factorsAccessory proteins work to alter the cytoskeleton behaviorActin filament behavior is regulated by two major classes of binding proteins: those that bind along the side of a filament and those that bind to the ends.Examples include:Capping proteins that plug either the plus and minus endSide-binders that stabilize or destabilize the cytoskeleton or act to cross-linkSevering proteins that cut filaments in the middle to generate new endsCytoskeletal capping proteins - ActinCapping proteins bind to the ends offilamentsThey can change the dynamics of filaments:since + end is more dynamic; capping canblock growth or shrinkage.Examples: CapZ and tropomodulinrespectively cap the + and - ends of actin inmuscle to make very stable actin filamentsin sarcomeresCapZ stabilizes an actin filament at its plusend by rendering it inactiveEnd binding proteins can affect filament dynamics even when they are present at very low levelsCytoskeletal capping proteins – MicrotubulesCapping proteins of microtubule + ends are called plus-end tracking proteins (+TIPs) – affects dynamic instability.