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http://purl.uniprot.org/citations/37058288http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37058288http://www.w3.org/2000/01/rdf-schema#comment"Lysosomal integrity is vital for cell homeostasis, but the underlying mechanisms are poorly understood. Here, we identify CLH-6, the C. elegans ortholog of the lysosomal Cl-/H+ antiporter ClC-7, as an important factor for protecting lysosomal integrity. Loss of CLH-6 affects lysosomal degradation, causing cargo accumulation and membrane rupture. Reducing cargo delivery or increasing CPL-1/cathepsin L or CPR-2/cathepsin B expression suppresses these lysosomal defects. Inactivation of CPL-1 or CPR-2, like CLH-6 inactivation, affects cargo digestion and causes lysosomal membrane rupture. Thus, loss of CLH-6 impairs cargo degradation, leading to membrane damage of lysosomes. In clh-6(lf) mutants, lysosomes are acidified as in wild type but contain lower chloride levels, and cathepsin B and L activities are significantly reduced. Cl-binds to CPL-1 and CPR-2 in vitro, and Cl-supplementation increases lysosomal cathepsin B and L activities. Altogether, these findings suggest that CLH-6 maintains the luminal chloride levels required for cathepsin activity, thus facilitating substrate digestion to protect lysosomal membrane integrity."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.org/dc/terms/identifier"doi:10.1083/jcb.202210063"xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/author"Li M."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/author"Zhang Q."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/author"Jian Y."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/name"J Cell Biol"xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/pages"e202210063"xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/title"Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation."xsd:string
http://purl.uniprot.org/citations/37058288http://purl.uniprot.org/core/volume"222"xsd:string
http://purl.uniprot.org/citations/37058288http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37058288
http://purl.uniprot.org/citations/37058288http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37058288
http://purl.uniprot.org/uniprot/#_G5EC75-mappedCitation-37058288http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37058288
http://purl.uniprot.org/uniprot/G5EC75http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/37058288