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


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.

SUBMITTER: Buckley CM 

PROVIDER: S-EPMC5056073 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Buckley Catherine M CM   Gopaldass Navin N   Bosmani Cristina C   Johnston Simon A SA   Soldati Thierry T   Insall Robert H RH   King Jason S JS  

Proceedings of the National Academy of Sciences of the United States of America 20160919 40


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) compl  ...[more]

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