Counterregulation of CAMP-directed Kinase Activities Controls Ciliogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Mar 28

PMID 29581457

Citations 27

Authors

Monia Porpora

Simona Sauchella

Laura Rinaldi

Rossella Delle Donne

Maria Sepe

Omar Torres-Quesada

Daniela Intartaglia

Corrado Garbi

Luigi Insabato

Margherita Santoriello

Verena A Bachmann

Matthis Synofzik

Herbert H Lindner

Ivan Conte

Eduard Stefan

Antonio Feliciello

Affiliations

Soon will be listed here.

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 ubiquitin-proteasome system, thereby controlling essential aspects of ciliogenesis.

Citing Articles

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NEKL-4 regulates microtubule stability and mitochondrial health in ciliated neurons.

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Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA-protein interactions.

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Illumination of understudied ciliary kinases.

Flax R, Rosston P, Rocha C, Anderson B, Capener J, Durcan T Front Mol Biosci. 2024; 11:1352781.

PMID: 38523660 PMC: 10958382. DOI: 10.3389/fmolb.2024.1352781.

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