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

Abstract : 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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https://hal.sorbonne-universite.fr/hal-03020853
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Submitted on : Tuesday, November 24, 2020 - 9:42:15 AM
Last modification on : Wednesday, February 24, 2021 - 12:30:03 PM
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Julie Stoufflet, Maxime Chaulet, Mohamed Doulazmi, Coralie Fouquet, Caroline Dubacq, et al.. Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration. Science Advances , American Association for the Advancement of Science (AAAS), 2020, 6 (36), ⟨10.1126/sciadv.aba3992⟩. ⟨hal-03020853⟩

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