Title: Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC‐7
Abstract: The FASEB JournalVolume 23, Issue 12 p. 4056-4068 Research CommunicationFree to Read Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC-7 Lena Wartosch, Lena Wartosch Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany Freie Universität, Berlin, GermanySearch for more papers by this authorJens C. Fuhrmann, Jens C. Fuhrmann Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany Metanomics GmbH, Tegeler Weg 33, D-10589 Berlin, GermanySearch for more papers by this authorMichaela Schweizer, Michaela Schweizer Zentrum für Molekulare Neurobiologie (ZMNH), Universität Hamburg, Hamburg, GermanySearch for more papers by this authorTobias Stauber, Tobias Stauber Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, GermanySearch for more papers by this authorThomas J. Jentsch, Corresponding Author Thomas J. Jentsch [email protected] Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, GermanyCorrespondence. Leibniz-Institut für Molekulare Pharmakologie and Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13125 Berlin, Germany. E-mail: [email protected]Search for more papers by this author Lena Wartosch, Lena Wartosch Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany Freie Universität, Berlin, GermanySearch for more papers by this authorJens C. Fuhrmann, Jens C. Fuhrmann Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany Metanomics GmbH, Tegeler Weg 33, D-10589 Berlin, GermanySearch for more papers by this authorMichaela Schweizer, Michaela Schweizer Zentrum für Molekulare Neurobiologie (ZMNH), Universität Hamburg, Hamburg, GermanySearch for more papers by this authorTobias Stauber, Tobias Stauber Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, GermanySearch for more papers by this authorThomas J. Jentsch, Corresponding Author Thomas J. Jentsch [email protected] Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, GermanyCorrespondence. Leibniz-Institut für Molekulare Pharmakologie and Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13125 Berlin, Germany. E-mail: [email protected]Search for more papers by this author First published: 06 August 2009 https://doi.org/10.1096/fj.09-130880Citations: 60Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT Mutations in either ClC-7, a late endoso- mal/lysosomal member of the CLC family of chloride channels and transporters, or in its β-subunit Ostm1 cause osteopetrosis and lysosomal storage disease in mice and humans. The severe phenotype of mice globally deleted for ClC-7 or Ostm1 and the absence of storage material in cultured cells hampered investiga- tions of the mechanism leading to lysosomal pathology in the absence of functional ClC-7/Ostm1 transporters. Tissue-specific ClC-7-knockout mice now reveal that accumulation of storage material occurs cell-autono- mously in neurons or renal proximal tubular cells lacking ClC-7. Almost all ClC-7-deficient neurons die. The activation of glia is restricted to brain regions where ClC-7 has been inactivated. The effect of ClC-7 disruption on lysosomal function was investigated in renal proximal tubular cells, which display high endo- cytotic activity. Pulse-chase endocytosis experiments in vivo with mice carrying chimeric deletion of ClC-7 in proximal tubules allowed a direct comparison of the handling of endocytosed protein between cells express- ing or lacking ClC-7. Whereas protein was endocytosed similarly in cells of either genotype, its half-life in- creased significantly in ClC-7-deficient cells. These ex- periments demonstrate that lysosomal pathology is a cell-autonomous consequence of ClC-7 disruption and that ClC-7 is important for lysosomal protein degrada- tion.—Wartosch, L., Fuhrmann, J. C., Schweizer, M., Stauber, T., Jentsch, T. J. Lysosomal degradation of endocytosed proteins depends on the chloride trans- port protein ClC-7. 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Publication Year: 2009
Publication Date: 2009-08-06
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 82
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