Article (Scientific journals)
Modulation of ciliary phosphoinositide content regulates trafficking and Sonic hedgehog signaling output
Chavez, M; Van Sande, J; de Kerchove d'Exaerde, A et al.
2015In Developmental Cell, 34, p. 338-350
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Keywords :
primary cilium; phosphoinositide; phosphatase
Abstract :
[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 :
34
Pages :
338-350
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 July 2015

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