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A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi

Stoetzel, Corinne; Bär, Séverine; De Craene, Johan-Owen; Scheidecker, Sophie; Etard, Christelle 1; Chicher, Johana; Reck, Jennifer R.; Perrault, Isabelle; Geoffroy, Véronique; Chennen, Kirsley; Strähle, Uwe 2; Hammann, Philippe; Friant, Sylvie; Dollfus, Hélène
1 Karlsruher Institut für Technologie (KIT)
2 Universität Karlsruhe (TH) – Campus Nord (CN)

Abstract:

Ciliopathies are a group of diseases that affect kidney and retina among other organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary processes in zebrafish. Furthermore, we demonstrate its interaction with the golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation impairs Golgi trafficking functions in humanized yeast cells. Moreover, in VPS15-R998Q patient fibroblasts, the intraflagellar transport protein IFT20 is not localized to vesicles trafficking to the cilium but is restricted to the Golgi. Our findings suggest that at the Golgi, VPS15 and GM130 form a protein complex devoid of VPS34 to ensure the IFT20-dependent sorting and transport of membrane proteins from the cis-Golgi to the primary cilium.


Volltext §
DOI: 10.5445/IR/1000062473
Originalveröffentlichung
DOI: 10.1038/ncomms13586
Scopus
Zitationen: 47
Web of Science
Zitationen: 45
Dimensions
Zitationen: 50
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2016
Sprache Englisch
Identifikator ISSN: 2041-1723
urn:nbn:de:swb:90-624733
KITopen-ID: 1000062473
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Nature Communications
Verlag Nature Research
Band 7
Seiten Art. Nr. 13586
Vorab online veröffentlicht am 24.11.2016
Schlagwörter Ciliogenesis, Disease genetics, Golgi, Mechanisms of disease
Nachgewiesen in Scopus
Web of Science
Dimensions
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