Article (Scientific journals)
Mutations in the inositol polyphosphate-5-phosphatase E gene link phosphatidyl inositol signaling to the ciliopathies
Bielas, S. L.; Silhavy, J. L.; Brancati, F. et al.
2009In Nature Genetics, 41, p. 1032-1036
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Keywords :
ciliopathies; mutations; phosphatidyl inosito; inositol polyphosphate-5-phosphatase
Abstract :
[en] Phosphotidylinositol (PtdIns) signaling is tightly regulated both spatially and temporally by subcellularly localized PtdIns kinases and phosphatases that dynamically alter downstream signaling events1. Joubert syndrome is characterized by a specific midbrain-hindbrain malformation (‘molar tooth sign’), variably associated retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly2 and is included in the newly emerging group of ‘ciliopathies’. In individuals with Joubert disease genetically linked to JBTS1, we identified mutations in the INPP5E gene, encoding inositol polyphosphate-5-phosphatase E, which hydrolyzes the 5-phosphate of PtdIns(3,4,5)P3 and PtdIns(4,5)P2. Mutations clustered in the phosphatase domain and impaired 5-phosphatase activity, resulting in altered cellular PtdIns ratios. INPP5E localized to cilia in major organs affected by Joubert syndrome, and mutations promoted premature destabilization of cilia in response to stimulation. These data link PtdIns signaling to the primary cilium, a cellular structure that is becoming increasingly recognized for its role in mediating cell signals and neuronal function
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Bielas, S. L.;  University of California, San Diego, La Jolla, USA
Silhavy, J. L.;  University of California, San Diego, La Jolla, USA
Brancati, F.;  Casa Sollievo della Sofferenza-Mendel Institute, Casa Sollievo della Sofferenza Hospital, Rome, Italy
Kisseleva, M. V.;  Washington University School of Medicine, St. Louis, Missouri, USA
Al-Gazali, L.;  United Arab Emirates University, Faculty of Medicine and Health Sciences, Al Ain, United Arab Emirates
Sztriha, L.;  University of Szeged, Szeged, Hungary
Bayoumi, R. A.;  College of Medicine, Sultan Qaboos University, Al-Khoud, Sultanate of Oman
Zaki, M. S.;  National Research Centre, Dokki, Cairo, Egypt
Abdel-Aleem, A.;  National Research Centre, Dokki, Cairo, Egypt
Rosti, O.;  Istanbul University
Kayserili, H.;  Istanbul University
Swistun, D.;  University of California, San Diego, La Jolla, USA
Scott, L. C.;  University of California, San Diego, La Jolla, USA
Bertini, E.;  Unit of Molecular Medicine, Department of Laboratory Medicine, Bambino Gesu Children’s Research Hospital, Rome, Italy
Boltshauser, E.;  University Children’s Hospital of Zurich, Zurich, Switzerland > Department of Paediatric Neurology
Fazzi, Elisa;  Department of Child Neurology and Psychiatry, C. Mondino, Pavia, Italy
Travaglini, L.
Field, S. J.;  University of California, San Diego, La Jolla, USA
Gayral, S.
Jacoby, M.;  Université Libre de Bruxelles - ULB > Institut de Biologie et de Médecine Moléculaires (IBMM)
Schurmans, Stéphane  ;  Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire
Dallapiccola, B.;  Department of Experimental Medicine, Sapienza University, Rome, Italy
Majerus, P. W.
Valente, E. M.;  University of Messina, Messina, Italy
Gleeson, J. G.;  University of California, San Diego, La Jolla, USA
More authors (15 more) Less
Language :
English
Title :
Mutations in the inositol polyphosphate-5-phosphatase E gene link phosphatidyl inositol signaling to the ciliopathies
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 :
1032-1036
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 10 December 2009

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