title: Activation of nucleation promoting factors for directional actin filament elongation: allosteric regulation and multimerization on the membrane.
abstract: Nucleation promoting factors (NPFs) activate the Arp2/3 complex to produce branched actin filaments. Branched actin filaments are observed in most organelles, and specific NPFs, such as WASP, N-WASP, WAVEs, WASH, and WHAMM, exist for each organelle. Interestingly, Arp2/3 and NPFs are both inactive by themselves, and thus require activation. The exposure of the Arp2/3 activating region, the VCA fragment, is recognized to be a key event in the activation of the NPFs. Together, small GTPase binding, phosphorylation, SH3 binding, and membrane binding promote VCA exposure synergistically. The increase in the local concentration of NPF by multimerization is thought to occur with the combination of such activators, to maximally activate the NPF and confine the region of actin polymerization. The mechanism of uni-directional filament extension beneath the membrane also is discussed.
authors: Laboratory of Membrane and Cytoskeleton Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. suetsugu@iam.u-tokyo.ac.jp
authors: Shiro
authors: S
authors: Suetsugu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000494:Allosteric Regulation; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D055503:Protein Multimerization; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D051316:Wiskott-Aldrich Syndrome Protein