{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shipman KE"],"funding":["NIDDK NIH HHS","NIH HHS"],"pagination":["619-640"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10103310"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["34(4)"],"pubmed_abstract":["<h4>Significance statement</h4>Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease causes an unknown impairment in endocytic traffic, leading to tubular proteinuria. The authors integrated data from biochemical and quantitative imaging studies in proximal tubule cells into a mathematical model to determine that loss of ClC-5 impairs endosome acidification and delays early endosome maturation in proximal tubule cells, resulting in reduced megalin recycling, surface expression, and half-life. Studies in a Dent mouse model also revealed subsegment-specific differences in the effects of ClC-5 knockout on proximal tubule subsegments. The approach provides a template to dissect the effects of mutations or perturbations that alter tubular recovery of filtered proteins from the lev"],"journal":["Journal of the American Society of Nephrology : JASN"],"pubmed_title":["Impaired Endosome Maturation Mediates Tubular Proteinuria in Dent Disease Cell Culture and Mouse Models."],"pmcid":["PMC10103310"],"funding_grant_id":["T32 DK007052","R01 DK118726","F31 DK121394","P30 DK079307","S10 OD028596","S10 OD021627","R01 DK125049"],"pubmed_authors":["Edwards A","Gerges M","Kashlan OB","Weisz OA","Rbaibi Y","Shipman KE","Tan RJ","Baty CJ","Long KR","Cowan IA","Marciszyn AL"],"additional_accession":[]},"is_claimable":false,"name":"Impaired Endosome Maturation Mediates Tubular Proteinuria in Dent Disease Cell Culture and Mouse Models.","description":"<h4>Significance statement</h4>Loss of function of the 2Cl - /H + antiporter ClC-5 in Dent disease causes an unknown impairment in endocytic traffic, leading to tubular proteinuria. The authors integrated data from biochemical and quantitative imaging studies in proximal tubule cells into a mathematical model to determine that loss of ClC-5 impairs endosome acidification and delays early endosome maturation in proximal tubule cells, resulting in reduced megalin recycling, surface expression, and half-life. Studies in a Dent mouse model also revealed subsegment-specific differences in the effects of ClC-5 knockout on proximal tubule subsegments. The approach provides a template to dissect the effects of mutations or perturbations that alter tubular recovery of filtered proteins from the lev","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-07-16T09:27:24.066Z","creation":"2025-04-05T14:43:59.949Z"},"accession":"S-EPMC10103310","cross_references":{"pubmed":["36758125"],"doi":["10.1681/ASN.0000000000000084","10.1681/asn.0000000000000084"]}}