title: Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis.
abstract: Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.
authors.affiliation: 1] Division of Genetics and Cell Biology, Dulbecco Telethon Institute (DTI) at Dibit, San Raffaele Scientific Institute, Via Olgettina, 58, 20132 Milan, Italy [2] Ph.D. Program in Molecular and Cellular Biology, Vita-Salute San Raffaele University, Via Olgettina, 58, 20132 Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Castelli
authors.forename: Manila
authors.initials: M
authors.lastname: Boca
authors.forename: Marco
authors.initials: M
authors.lastname: Chiaravalli
authors.forename: Harini
authors.initials: H
authors.lastname: Ramalingam
authors.forename: Isaline
authors.initials: I
authors.lastname: Rowe
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Distefano
authors.forename: Thomas
authors.initials: T
authors.lastname: Carroll
authors.forename: Alessandra
authors.initials: A
authors.lastname: Boletta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002465:Cell Movement; D016764:Cell Polarity; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000172:deficiency / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D051571:Protein Kinase C-alpha; D050396:TRPP Cation Channels; C115084:Pard3 protein, mouse