GSBS Student Publications

Title

Hierarchical regulation of WASP/WAVE proteins

Publication Date

2008-11-11

UMMS Affiliation

Department of Molecular Genetics and Microbiology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

DOI of Published Version

10.1016/j.molcel.2008.10.012

Source

Mol Cell. 2008 Nov 7;32(3):426-38. Link to article on publisher's site

Journal/Book/Conference Title

Molecular cell

Related Resources

Link to Article in PubMed

PubMed ID

18995840

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