Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration

The primary cilium (PC) is a small centrosome-assembled organelle, protruding from the surface of most eukaryotic cells. It plays a key role in cell migration, but the underlying mechanisms are unknown. Here, we show that the PC regulates neuronal migration via cyclic adenosine 3’-5’ monosphosphate...

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Detalles Bibliográficos
Autores principales: Stoufflet, Julie, Chaulet, Maxime, Doulazmi, Mohamed, Fouquet, Coralie, Dubacq, Caroline, Métin, Christine, Schneider-Maunoury, Sylvie, Trembleau, Alain, Vincent, Pierre, Caillé, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467704/
https://www.ncbi.nlm.nih.gov/pubmed/32917588
http://dx.doi.org/10.1126/sciadv.aba3992
Descripción
Sumario:The primary cilium (PC) is a small centrosome-assembled organelle, protruding from the surface of most eukaryotic cells. It plays a key role in cell migration, but the underlying mechanisms are unknown. Here, we show that the PC regulates neuronal migration via cyclic adenosine 3’-5’ monosphosphate (cAMP) production activating centrosomal protein kinase A (PKA). Biosensor live imaging revealed a periodic cAMP hotspot at the centrosome of embryonic, postnatal, and adult migrating neurons. Genetic ablation of the PC, or knockdown of ciliary adenylate cyclase 3, caused hotspot disappearance and migratory defects, with defective centrosome dynamics and altered nucleokinesis. Delocalization of PKA from the centrosome phenocopied the migratory defects. Our results show that the PC and centrosome form a single cAMP signaling unit dynamically regulating migration, further highlighting the centrosome as a signaling hub.

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