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- Title
Counterregulation of cAMP-directed kinase activities controls ciliogenesis.
- Authors
Porpora, Monia; Sauchella, Simona; Rinaldi, Laura; Delle Donne, Rossella; Sepe, Maria; Torres-Quesada, Omar; Intartaglia, Daniela; Garbi, Corrado; Insabato, Luigi; Santoriello, Margherita; Bachmann, Verena A.; Synofzik, Matthis; Lindner, Herbert H.; Conte, Ivan; Stefan, Eduard; Feliciello, Antonio
- Abstract
The primary cilium emanates from the cell surface of growth-arrested cells and plays a central role in vertebrate development and tissue homeostasis. The mechanisms that control ciliogenesis have been extensively explored. However, the intersection between GPCR signaling and the ubiquitin pathway in the control of cilium stability are unknown. Here we observe that cAMP elevation promotes cilia resorption. At centriolar satellites, we identify a multimeric complex nucleated by PCM1 that includes two kinases, NEK10 and PKA, and the E3 ubiquitin ligase CHIP. We show that NEK10 is essential for ciliogenesis in mammals and for the development of medaka fish. PKA phosphorylation primes NEK10 for CHIP-mediated ubiquitination and proteolysis resulting in cilia resorption. Disarrangement of this control mechanism occurs in proliferative and genetic disorders. These findings unveil a pericentriolar kinase signalosome that efficiently links the cAMP cascade with the ubiquitinproteasome system, thereby controlling essential aspects of ciliogenesis.
- Subjects
MAMMAL development; CYCLIC-AMP-dependent protein kinase; UBIQUITINATION; CELL membranes; FISH development; CILIA &; ciliary motion; GENETIC disorders
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-03643-9