Format

Send to

Choose Destination
Dev Cell. 2013 Jan 28;24(2):169-81. doi: 10.1016/j.devcel.2012.12.014.

Cyclical action of the WASH complex: FAM21 and capping protein drive WASH recycling, not initial recruitment.

Author information

1
CR-UK Beatson Institute for Cancer Research, Glasgow University, Switchback Road, Glasgow G61 1BD, UK.

Abstract

WASH causes actin to polymerize on vesicles involved in retrograde traffic and exocytosis. It is found within a regulatory complex, but the physiological roles of the other four members are unknown. Here we present genetic analysis of the subunits' individual functions in Dictyostelium. Mutants in each subunit are completely blocked in exocytosis. All subunits except FAM21 are required to drive actin assembly on lysosomes. Without actin, lysosomes never recycle vacuolar-type H(+)-adenosine triphosphatase (V-ATPase) or neutralize to form postlysosomes. However, in FAM21 knockout lysosomes, WASH generates excessive, dynamic streams of actin. These successfully remove V-ATPase, neutralize, and form huge postlysosomes. The distinction between WASH and FAM21 phenotypes is conserved in human cells. Thus, FAM21 and WASH act at different steps of a cyclical pathway in which FAM21 mediates recycling of the complex back to acidic lysosomes. Recycling is driven by FAM21's interaction with capping protein, which couples the WASH complex to dynamic actin on vesicles.

PMID:
23369714
DOI:
10.1016/j.devcel.2012.12.014
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center