title: Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure.
abstract: Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage in vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1(V/V)) that expresses noncleavable PC1. The Pkd1(V/V) mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wild-type mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules in vivo.
authors.affiliation: Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Yu
authors.forename: Karl
authors.initials: K
authors.lastname: Hackmann
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
authors.forename: Jianggang
authors.initials: J
authors.lastname: Gao
authors.forename: Xiaobing
authors.initials: X
authors.lastname: He
authors.forename: Klaus
authors.initials: K
authors.lastname: Piontek
authors.forename: Miguel A
authors.initials: MA
authors.lastname: García-González
authors.forename: Miguel A
authors.initials: MA
authors.lastname: García González
authors.forename: Luis F
authors.initials: LF
authors.lastname: Menezes
authors.forename: Hangxue
authors.initials: H
authors.lastname: Xu
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002478:Cells, Cultured; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; D050396:TRPP Cation Channels