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Alexis Gautreau“The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex.”

Abstract :

The Arp2/3 complex generates branched actin networks when activated by Nucleation Promoting Factors (NPFs). Recently, the WASH family of NPFs has been identified but its cellular role is unknown. Here we show that WASH is localized on a microdomain of sorting and recycling endosomes. WASH depletion gives rise to narrow membrane tubules spreading out from these organelles along microtubules. WASH recruits directly Dynamin, the inhibition of which phenocopies WASH depletion. We purified WASH to understand its regulation. WASH belongs to a novel multiprotein complex containing at least seven subunits, including the heterodimer of capping protein (CP). Controlling elongation of actin filaments is known to tune the force generated by polymerization of branched actin networks. The unprecedented integration of an NPF and CP within the same molecular machine might provide the coordination of these otherwise antagonistic activities required to generate the membrane tension facilitating fission by Dynamin.

Selected publications

Derivery E, Lombard B, Loew D, Gautreau A.
The Wave complex is intrinsically inactive.
Cell Motil Cytoskeleton. 2009 Feb 10.    
Derivery E, Fink J, Martin D, Houdusse A, Piel M, Stradal TE, Louvard D, Gautreau A.
Free Brick1 is a trimeric precursor in the assembly of a functional wave complex. PLoS ONE. 2008 Jun 18;3(6):e2462.
Bouslama-Oueghlani L, Echard A, Louvard D, Gautreau A. RNAi depleted Drosophila cell extracts to dissect signaling pathways leading to actin polymerization. J Biochem Biophys Methods. 2007 Jun 10;70(4):663-9.    
Gautreau A, Ho HY, Li J, Steen H, Gygi SP, Kirschner MW. Purification and architecture of the ubiquitous Wave complex. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4379-83.