WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion

King, Jason; Gueho, Aurélie; Hagedorn, Monica; Gopaldass, Navin Andréw; Leuba, Florence; Soldati, Thierry; Insall, Robert H.

doi:10.1091/mbc.e13-02-0092

Cited by 85 publications

(90 citation statements)

References 66 publications

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“…This defect was less pronounced with Klebsiella aerogenes (Fig. 9B), consistent with the milder growth defect previously reported (30). To analyze phagocytosis in more detail, we also investigated the ability of WASH-null cells to engulf fluorescently labeled yeast.…”

Section: Wash Drives Recycling Of Surface Proteins From Early Macropisupporting

confidence: 88%

“…Reduction in the surface levels of proteins such as SibC should affect the ability of cells to bind bacteria (52). Previously, we showed that WASHnull cells grow poorly on bacteria, despite normal axenic growth (27,30). As phagocytosis, but not macropinocytosis, is dependent on plasma membrane receptors, we measured the rate of bacterial uptake in WASH-null cells.…”

Section: Wash Drives Recycling Of Surface Proteins From Early Macropimentioning

confidence: 98%

“…2C). Indeed, phagosomal acidification was actually slightly decreased, most likely due to decreased V-ATPase supply, as so much is sequestered in later compartments such as postlysosomes (27,30 mammalian cells, WASH mediates sorting from endosomes via direct interaction between the FAM21 subunit of the WASH complex and the VPS35 subunit of the retromer sorting complex (24,32,36). The retromer complex drives extraction of specific proteins at several trafficking steps by sequence-specific binding (37)(38)(39).…”

Section: Wash Is Recruited To Early Macropinosomes and Phagosomesmentioning

confidence: 99%

“…In particular, significant progress has been made in defining the role of actin in the segregation and extraction of specific proteins (22). Many studies describe a role for the WASH (WASP and SCAR homolog) complex in driving endosomal actin polymerization (23)(24)(25)(26)(27)(28)(29)(30). WASH has been implicated in the endosome-to-surface trafficking of a number of cargos, including the transferrin receptor (TfnR), α5β1 integrins,…”

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confidence: 99%

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

Buckley

Gopaldass

Bosmani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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.phagocytosis | macropinocytosis | WASH | Dictyostelium | trafficking

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Section: Wash Drives Recycling Of Surface Proteins From Early Macropisupporting

confidence: 88%

Section: Wash Drives Recycling Of Surface Proteins From Early Macropimentioning

confidence: 98%

Section: Wash Is Recruited To Early Macropinosomes and Phagosomesmentioning

confidence: 99%

mentioning

confidence: 99%

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

Buckley

Gopaldass

Bosmani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Wild-type Dictyostelium cells (Ax2) were axenically cultivated in HL5c medium (Formedium) at 22°C. The Dictyostelium atg1− cells were described (34) and racH− cells from F. Rivero (University of Hull, Hull, United Kingdom). Dictyostelium mutants atg5−, atg6−, and atg7− were received from dictyBase (www.dictybase.org).…”

Section: Methodsmentioning

confidence: 99%

The autophagic machinery ensures nonlytic transmission of mycobacteria

Gerstenmaier

Pilla

Herrmann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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In contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. Previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an F-actin based structure, called the ejectosome. How the host cell maintains integrity of its plasma membrane during the ejection process was unknown. Here, we reveal an unexpected function for the autophagic machinery in nonlytic spreading of bacteria. We show that ejecting mycobacteria are escorted by a distinct polar autophagocytic vacuole. If autophagy is impaired, cell-to-cell transmission is inhibited, the host plasma membrane becomes compromised and the host cells die. These findings highlight a previously unidentified, highly ordered interaction between bacteria and the autophagic pathway and might represent the ancient way to ensure nonlytic egress of bacteria.autophagy | Dictyostelium discoideum | Mycobacterium marinum | ejection

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Actin dynamics in host–pathogen interaction

Stradal

Schelhaas

2018

FEBS Letters

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The actin cytoskeleton and Rho GTPase signaling to actin assembly are prime targets of bacterial and viral pathogens, simply because actin is involved in all motile and membrane remodeling processes, such as phagocytosis, macropinocytosis, endocytosis, exocytosis, vesicular trafficking and membrane fusion events, motility, and last but not least, autophagy. This article aims at providing an overview of the most prominent pathogen‐induced or ‐hijacked actin structures, and an outlook on how future research might uncover additional, equally sophisticated interactions.

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WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion

Cited by 85 publications

References 66 publications

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

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

The autophagic machinery ensures nonlytic transmission of mycobacteria

Actin dynamics in host–pathogen interaction

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