Article (Scientific journals)
INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse
Jacoby, Monique; Cox, James J.; Gayral, Stéphanie et al.
2009In Nature Genetics, 41, p. 1027-1031
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Keywords :
INPP5E; cilium signaling defects; ciliopathies; human; mouse
Abstract :
[en] The primary cilium is an antenna-like structure that protrudes from the cell surface of quiescent/differentiated cells and participates in extracellular signal processing1–3. 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 a (PDGFRa) 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Jacoby, Monique;  Université Libre de Bruxelles - ULB
Cox, James J.;  Cambridge Institute of Medical Research, Wellcome/MRC Building, Addenbrooke’s Hospital, Cambridge, UK
Gayral, Stéphanie;  Université Libre de Bruxelles - ULB
Hampshire, Daniel J.;  School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK
Ayub, Mohammed;  4Psychiatry of Learning Disability, St. Lukes Hospital, Middlesbrough, UK
Blockmans, Marianne;  Université Libre de Bruxelles - ULB
Pernot, Eileen;  Université Libre de Bruxelles - ULB
Kisseleva, Marina V.;  Université Libre de Bruxelles - ULB
Compère, Philippe ;  Université de Liège - ULiège > Département des sciences et gestion de l'environnement > Département des sciences et gestion de l'environnement
Schiffmann, Serge N;  Université Libre de Bruxelles - ULB
Gergely, Fanni;  8Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
Riley, John H.;  9GSK Respiratory Medicines Development Centre, Stockley Park, Uxbridge, UK
Pérez-Morga, David;  Université Libre de Bruxelles - ULB
Woods, C. Geoffrey
Schurmans, Stéphane  ;  Université Libre de Bruxelles - ULB > 15Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire
More authors (5 more) Less
Language :
English
Title :
INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse
Publication date :
2009
Journal title :
Nature Genetics
ISSN :
1061-4036
eISSN :
1546-1718
Publisher :
Nature Publishing Group, New York, United States - New York
Volume :
41
Pages :
1027-1031
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 10 December 2009

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