Interaction of smoothened with integrin-linked kinase in primary cilia mediates Hedgehog signalling

Here we report that ILK localizes in the mouse primary cilium, a sensory organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway effector smoothened (Smo) and suppresses the induction of Gli transcript...

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Bibliographic Details
Published in:EMBO reports 2013-09, Vol.14 (9), p.837-844
Main Authors: Barakat, Badia, Yu, Liang, Lo, Camden, Vu, Duc, De Luca, Elisabetta, Cain, Jason E, Martellotto, Luciano G, Dedhar, Shoukat, Sadler, Anthony J, Wang, Die, Neil Watkins, D, Hannigan, Gregory E
Format: Article
Language:English
Subjects:
Animals
Arrestins - metabolism
Cell Line
Cellular biology
cerebellar development
Cerebellum - embryology
Cerebellum - metabolism
Cilia - metabolism
Developmental biology
EMBO37
Hedgehog Proteins - metabolism
Hedgehog signalling
integrin-linked kinase
Kinases
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Mice
primary cilium
Protein Kinase Inhibitors - pharmacology
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Scientific Report
Scientific Reports
Signal Transduction
Smoothened Receptor
Zinc Finger Protein Gli2
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Summary:Here we report that ILK localizes in the mouse primary cilium, a sensory organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway effector smoothened (Smo) and suppresses the induction of Gli transcription factor mRNAs by SHh. Conditional deletion of ILK or Smo also inhibits SHh‐driven activation of Gli2 in the embryonic mouse cerebellum. ILK regulation of Hh signalling probably requires the physical interaction of ILK and Smo in the cilium, and we also show selective cilia‐associated interaction of ILK with β‐arrestin, a known mediator of Smo‐dependent signalling. The protein kinase ILK promotes the movement of Smoothened into the mouse primary cilium and is required for the induction of Gli transcription factors in response to Sonic Hedgehog.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2013.110