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

Park, L., Thomason, P.A., Zech, T., King, J.S., Veltman, D.M., Carnell, M., Ura, S., Machesky, L.M. and Insall, R.H. (2013) Cyclical Action of the WASH complex: FAM21 and capping protein drive WASH recycling, not initial recruitment. Developmental Cell, 24(2), pp. 169-181. (doi:10.1016/j.devcel.2012.12.014)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zech, Mr Tobias and Machesky, Professor Laura and Ura, Mr Seiji and Insall, Professor Robert and King, Dr Jason and Carnell, Mr Michael and Thomason, Dr Peter and Park, Ms Laura
Authors: Park, L., Thomason, P.A., Zech, T., King, J.S., Veltman, D.M., Carnell, M., Ura, S., Machesky, L.M., and Insall, R.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Developmental Cell
ISSN:1534-5807
ISSN (Online):1878-1551

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