Modulation of ciliary phosphoinositide content regulates trafficking and Sonic hedgehog signaling output

[en] Ciliary transport is required for ciliogenesis, signal transduction, and trafficking of receptors to the primary cilium. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) have been associated with ciliary dysfunction; however, its role in regulating ciliary phosphoinositides is unknown. Here we report that in neural stem cells, phosphatidylinositol 4-phosphate (PI4P) is found in high levels in cilia whereas phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is not detectable. Upon INPP5E inactivation, PI(4,5)P2 accumulates at the ciliary tip whereas PI4P is depleted. This is accompanied by recruitment of the PI(4,5)P2-interacting protein TULP3 to the ciliary membrane, along with Gpr161. This results in an increased production of cAMP and a repression of the Shh transcription gene Gli1. Our results reveal the link between ciliary regulation of phosphoinositides by INPP5E and Shh regulation via ciliary trafficking of TULP3/Gpr161 and also provide mechanistic insight into ciliary alterations found in Joubert and MORM syndromes resulting from INPP5E mutations.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Chavez, M

Van Sande, J

de Kerchove d'Exaerde, A

Schurmans, Stéphane ; Université de Liège > Département de sciences fonctionnelles (DSF) > Biochimie métabolique vétérinaire

Schiffmann, S

Language :

English

Title :

Modulation of ciliary phosphoinositide content regulates trafficking and Sonic hedgehog signaling output

Publication date :

2015

Journal title :

Developmental Cell

ISSN :

1534-5807

Publisher :

Elsevier Science

Volume :

Pages :

338-350

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 27 July 2015

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Scopus citations^®

196

Scopus citations^®
without self-citations

192

OpenCitations

215

OpenAlex citations

235

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