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Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

Maddalena Castelli; Manila Boca; Marco Chiaravalli; Harini Ramalingam; Isaline Rowe; Gianfranco Distefano; Thomas Carroll; Alessandra Boletta

(Profiled Author: Thomas J Carroll)

Nature Communications. 2013;4.

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. © 2013 Macmillan Publishers Limited. All rights reserved.


PMID: 24153433     PMCID: PMC3967097    

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