Molecular Cell
Volume 32, Issue 3, 7 November 2008, Pages 426-438
Journal home page for Molecular Cell

Article
Hierarchical Regulation of WASP/WAVE Proteins

https://doi.org/10.1016/j.molcel.2008.10.012Get rights and content
Under an Elsevier user license
open archive

Summary

Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.

PROTEINS
CELLBIO

Cited by (0)

4

These authors contributed equally to this work