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Lysosomal activity is, in turn, modulated by a complex network of over 200 membrane and accessory proteins that relay extracellular cues to these key degradation centers. The ClC-7 chloride (Cl\u2212)-proton (H+) antiporter (also known as CLCN7) is localized to the endolysosomal compartments and mutations in CLCN7 lead to osteopetrosis and neurodegeneration. Although the functions of ClC-7 have been extensively investigated in osteoclasts and neurons, its role in microglia in vivo remains largely unexamined. Here, we show that microglia and embryonic macrophages in zebrafish clcn7 mutants cannot effectively process extracellular debris in the form of apoptotic cells and \u03b2-amyloid. Despite these functional defects, microglia develop normally in clcn7 mutants and display normal expression of endosomal and lysosomal markers. We also find that mutants for ostm1, which encodes the \u03b2-subunit of ClC-7, have a phenotype that is strikingly similar to that of clcn7 mutants. Together, our observations uncover a previously unappreciated role of ClC-7 in microglia and contribute to the understanding of the neurodegenerative phenotypes that accompany mutations in this channel.<\/jats:p>","DOI":"10.1242\/jcs.261616","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T12:49:04Z","timestamp":1706705344000},"source":"Crossref","is-referenced-by-count":10,"title":["The Cl\u2212 transporter ClC-7 is essential for phagocytic clearance by microglia"],"prefix":"10.1242","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-0156","authenticated-orcid":false,"given":"Harini","family":"Iyer","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine Department of Developmental Biology , , Stanford, CA 94305 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-7472","authenticated-orcid":false,"given":"William S.","family":"Talbot","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Department of Developmental Biology , , Stanford, CA 94305 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"2024021614062659600_JCS261616C1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0009-8981(98)00183-1","article-title":"Elevated lysosomal pH in Mucolipidosis type IV cells","volume":"280","author":"Bach","year":"1999","journal-title":"Clin. 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