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

Julie Stoufflet (1, 2) , Maxime Chaulet (1) , Mohamed Doulazmi (2) , Coralie Fouquet (1) , Caroline Dubacq (1) , Christine Métin (3) , Sylvie Schneider-Maunoury (4) , Alain Trembleau (1) , Isabelle Caillé (1) , Pierre Vincent (2)

1 NPS - Neuroscience Paris Seine
2 B2A-IBPS - Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing
3 Institut du Fer à Moulin
4 LBD - Laboratoire de Biologie du Développement [IBPS]

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.

Domains: Neurons and Cognition [q-bio.NC]

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 , 2020, 6 (36), pp.eaba3992. ⟨10.1126/sciadv.aba3992⟩. ⟨hal-03020853⟩