PT  - JOURNAL ARTICLE
AU  - Julie Stoufflet
AU  - Maxime Chaulet
AU  - Mohamed Doulazmi
AU  - Coralie Fouquet
AU  - Caroline Dubacq
AU  - Christine Métin
AU  - Alain Trembleau
AU  - Pierre Vincent
AU  - Isabelle Caillé
TI  - Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration
AID  - 10.1101/765925
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 765925
4099  - http://biorxiv.org/content/early/2019/11/12/765925.short
4100  - http://biorxiv.org/content/early/2019/11/12/765925.full
AB  - 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 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 knock-down of ciliary Adenylate Cyclase 3, caused hotspot disappearance and migratory defects, with defective centrosome/nucleus coupling 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.The primary cilium regulates neuronal migration via cyclic AMP production activating Protein Kinase A at the centrosome