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Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis

Carnell, Michael; Zech, Tobias; Calaminus, Simon D.; Ura, Seiji; Hagedorn, Monica; Johnston, Simon A.; May, Robin C.; Soldati, Thierry; Machesky, Laura M.; Insall, Robert H.


Michael Carnell

Tobias Zech

Simon D. Calaminus

Seiji Ura

Monica Hagedorn

Simon A. Johnston

Robin C. May

Thierry Soldati

Laura M. Machesky

Robert H. Insall


WASP and SCAR homologue (WASH) is a recently identified and evolutionarily conserved regulator of actin polymerization. In this paper, we show that WASH coats mature Dictyostelium discoideum lysosomes and is essential for exocytosis of indigestible material. A related process, the expulsion of the lethal endosomal pathogen Cryptococcus neoformans from mammalian macrophages, also uses WASH-coated vesicles, and cells expressing dominant negative WASH mutants inefficiently expel C. neoformans. D. discoideum WASH causes filamentous actin (F-actin) patches to form on lysosomes, leading to the removal of vacuolar adenosine triphosphatase (V-ATPase) and the neutralization of lysosomes to form postlysosomes. Without WASH, no patches or coats are formed, neutral postlysosomes are not seen, and indigestible material such as dextran is not exocytosed. Similar results occur when actin polymerization is blocked with latrunculin. V-ATPases are known to bind avidly to F-actin. Our data imply a new mechanism, actin-mediated sorting, in which WASH and the Arp2/3 complex polymerize actin on vesicles to drive the separation and recycling of proteins such as the V-ATPase.


Carnell, M., Zech, T., Calaminus, S. D., Ura, S., Hagedorn, M., Johnston, S. A., …Insall, R. H. (2011). Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis. Journal of Cell Biology, 193(5), (831-839). doi:10.1083/jcb.201009119. ISSN 0021-9525

Journal Article Type Article
Online Publication Date May 23, 2011
Publication Date May 30, 2011
Print ISSN 0021-9525
Electronic ISSN 1540-8140
Publisher Rockefeller University Press
Peer Reviewed Peer Reviewed
Volume 193
Issue 5
Pages 831-839
Keywords Cell Biology
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