Hierarchical regulation of WASP/WAVE proteins.

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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Padrick SB,Cheng HC,Ismail AM,Panchal SC,Doolittle LK,Kim S,Skehan BM,Umetani J,Brautigam CA,Leong JM,Rosen MK

doi

10.1016/j.molcel.2008.10.012

subject

Has Abstract

pub_date

2008-11-07 00:00:00

pages

426-38

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00726-0

journal_volume

32

pub_type

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