Counterregulation of cAMP-directed kinase activities controls ciliogenesis
| Autor: | Porpora, Monia, Sauchella, Simona, Bachmann, Verena A, Synofzik, Matthis, Lindner, Herbert H, Conte, Ivan, Stefan, Eduard, Feliciello, Antonio, Rinaldi, Laura, Delle Donne, Rossella, Sepe, Maria, Torres-Quesada, Omar, Intartaglia, Daniela, Garbi, Corrado, Insabato, Luigi, Santoriello, Margherita |
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| Rok vydání: | 2016 |
| Předmět: |
animal structures
Science Ubiquitin-Protein Ligases PCM1 protein human Oryzias genetics [Hypogonadism] Cell Cycle Proteins genetics [NIMA-Related Kinases] metabolism [Cyclic AMP-Dependent Protein Kinases] Autoantigens Article metabolism [Cell Cycle Proteins] metabolism [Autoantigens] metabolism [Ubiquitin-Protein Ligases] metabolism [NIMA-Related Kinases] Nek10 protein human Animals Humans NIMA-Related Kinases Spinocerebellar Ataxias genetics [Spinocerebellar Ataxias] Cilia Phosphorylation lcsh:Science Cells Cultured STUB1 protein human Centrioles genetics [Ubiquitin-Protein Ligases] embryology [Oryzias] Hypogonadism Ubiquitination metabolism [Centrioles] physiology [NIMA-Related Kinases] Cyclic AMP-Dependent Protein Kinases HEK293 Cells Proteolysis metabolism [Cilia] lcsh:Q ddc:500 |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications 9(1), 1224 (2018). doi:10.1038/s41467-018-03643-9 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03643-9 |
| Popis: | 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 ubiquitin-proteasome system, thereby controlling essential aspects of ciliogenesis. The mechanisms that control ciliogenesis have been extensively explored however the signaling mechanisms that control cilium stability remain unclear. Here the authors show that GPCR signaling regulates cilia resorption via the ubiquitin-proteasome system. |
| Databáze: | OpenAIRE |
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