title: The role for HNF-1beta-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells.
abstract: Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1alpha, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1beta and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to gamma-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1beta and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1beta regulated genes.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yasuhara
authors.forename: Izumi
authors.initials: I
authors.lastname: Iseda
authors.forename: Jun
authors.initials: J
authors.lastname: Eguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukui
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Thomas
authors.initials: T
authors.lastname: Hiesberger
authors.forename: Peter
authors.initials: P
authors.lastname: Igarashi
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akagi
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Kanwar
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016764:Cell Polarity; D002923:Cilia / Q000502:physiology*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D051539:Hepatocyte Nuclear Factor 1-beta / Q000502:physiology*; D047468:Immunoprecipitation; D007685:Kidney Tubules, Collecting / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D034741:RNA, Small Interfering
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C504407:Tmem27 protein, mouse; D051539:Hepatocyte Nuclear Factor 1-beta