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INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse.

Jacoby, M. and Cox, J. J. and Gayral, S. and Hampshire, D. and Ayub, M. and Blockmans, M. and Pernot, E. and Kisseleva, M. V. and Compere, P. and Schiffmann, S. N. and Gergely, F. and Riley, D. and Perez-Morga, D. and Woods, C. G. and Schurmans, S. (2009) 'INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse.', Nature genetics., 41 (9). pp. 1027-1031.

Abstract

The primary cilium is an antenna-like structure that protrudes from the cell surface of quiescent/differentiated cells and participates in extracellular signal processing. Here, we report that mice deficient for the lipid 5-phosphatase Inpp5e develop a multiorgan disorder associated with structural defects of the primary cilium. In ciliated mouse embryonic fibroblasts, Inpp5e is concentrated in the axoneme of the primary cilium. Inpp5e inactivation did not impair ciliary assembly but altered the stability of pre-established cilia after serum addition. Blocking phosphoinositide 3-kinase (PI3K) activity or ciliary platelet-derived growth factor receptor (PDGFR) restored ciliary stability. In human INPP5E, we identified a mutation affecting INPP5E ciliary localization and cilium stability in a family with MORM syndrome, a condition related to Bardet-Biedl syndrome. Together, our results show that INPP5E plays an essential role in the primary cilium by controlling ciliary growth factor and PI3K signaling and stability, and highlight the consequences of INPP5E dysfunction.

Item Type:Article
Full text:Full text not available from this repository.
Publisher Web site:http://dx.doi.org/10.1038/ng.427
Record Created:01 Jul 2011 17:05
Last Modified:30 May 2012 15:25

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