Reference : INPP5E mutations cause primary cilium signaling defects, ciliary instability and cili...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Genetics & genetic processes
INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse
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 mailto [Université de Liège - ULg > 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 mailto [Université Libre de Bruxelles - ULB > 15Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire > > >]
Nature Genetics
Nature Publishing Group
Yes (verified by ORBi)
New York
[en] INPP5E ; cilium signaling defects ; ciliopathies ; human ; mouse
[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.
Researchers ; Professionals

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