Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 40, Pages E5906-E5915Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1524532113
Keywords
phagocytosis; macropinocytosis; WASH; Dictyostelium; trafficking
Categories
Funding
- Royal Society university research fellowship
- Cancer Research UK provided an Institute Group award
- Swiss National Science Foundation
- Medical Research Council
- Department for International Development Career Development Award Fellowship [MR/J009156/1]
- Krebs Institute fellowship
- Medical Research Foundation [R/140419]
- Wellcome Trust Strategic Award [097377/Z/11/Z]
- MRC [MR/J009156/1] Funding Source: UKRI
- Wellcome Trust [097377/Z/11/Z] Funding Source: Wellcome Trust
- Cancer Research UK [15672] Funding Source: researchfish
- Medical Research Council [MR/J009156/1] Funding Source: researchfish
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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.
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