WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley, C. M., Gopaldass, N., Bosmani, C., Johnston, S. A., Soldati, T., Insall, R. and King, J. S. (2016) WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors. Proceedings of the National Academy of Sciences of the United States of America, 113(40), E5906-E5915. (doi: 10.1073/pnas.1524532113) (PMID:27647881) (PMCID:PMC5056073)

Abstract

Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components.

• Item Type: Articles
• Additional Information: J.S.K. is supported by a Royal Society university research fellowship and Cancer Research UK provided an Institute Group award (to R.H.I.). The T.S. laboratory is supported by multiple grants from the Swiss National Science Foundation and T.S. is a member of iGE3 (www.ige3.unige.ch). S.A.J. is funded by the Medical Research Council, Department for International Development Career Development Award Fellowship MR/J009156/1, a Krebs Institute fellowship, Medical Research Foundation Grant R/140419, and Wellcome Trust Strategic Award 097377/Z/11/Z.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Insall, Professor Robert
• Authors: Buckley, C. M., Gopaldass, N., Bosmani, C., Johnston, S. A., Soldati, T., Insall, R., and King, J. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 10 September 2016
• Copyright Holders: Copyright © 2016 National Academy of Sciences
• First Published: First published in Proceedings of the National Academy of Sciences of the United States of America 113(40):E5906-E5915
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher