Jan 22, 2013

Endosomal recruitment of the WASH complex: active sequences and mutations impairing interaction with the retromer

Biology of the Cell
Emmanuèle HelferAlexis Gautreau

Abstract

The Wiskott-Aldrich syndrome protein and scar homolog (WASH) complex is the major Arp2/3 activator at the surface of endosomes. The branched actin network, that the WASH complex induces, contributes to cargo sorting and scission of transport intermediates destined for most endosomal routes. A major challenge is to understand how the WASH molecular machine is recruited to the surface of endosomes. The retromer endosomal machinery has been proposed by us and others to play a role in this process. In this work, we used an unbiased approach to identify the endosomal receptor of the WASH complex. We have delineated a short fragment of the FAM21 subunit that is able to displace the endogenous WASH complex from endosomes. Using a proteomic approach, we have identified the retromer cargo selective complex (CSC) as a partner of the active FAM21 sequence displacing the endogenous WASH complex. A point mutation in FAM21 that abolishes CSC interaction also impairs WASH complex displacement activity. The CSC is composed of three subunits, VPS35, VPS29 and VPS26. FAM21 directly binds the VPS35 subunit of the retromer CSC. Additionally, we show that a point mutant of VPS35 that blocks binding to VPS29 also prevents association with FAM21 and ...Continue Reading

  • References32
  • Citations25

References

Mentioned in this Paper

ACTR3
Actins
Tertiary Protein Structure
Vps26 protein, mouse
Plasma Protein Binding Capacity
FAM21 protein, mouse
Sorting - Cell Movement
Proteomics
ANGPTL2 gene
VPS29 protein, mouse

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