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 cAMP regulates cyclic saltatory neuronal migration at the centrosome
AID  - 10.1101/765925
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 765925
4099  - http://biorxiv.org/content/early/2019/09/13/765925.short
4100  - http://biorxiv.org/content/early/2019/09/13/765925.full
AB  - The primary cilium (PC) is crucial for neuronal migration but the underlying cellular mechanisms are mostly unknown. Here, we show that ciliary-produced cAMP present at the centrosome locally activates cAMP-dependent Protein Kinase A (PKA). We analyzed cAMP dynamics through biosensor live-imaging in cyclic saltatory migrating neurons of the mouse postnatal rostral migratory stream. This revealed a dynamic cAMP hotspot cyclically present at the centrosome, thus located at the basis of the PC. Genetic ablation of the PC and knock-down of the ciliary Adenylate Cyclase 3 lead to the hotspot disappearance. They also affect migration with defective centrosome/nucleus coupling leading to altered nucleokinesis, which is recapitulated by PKA genetic delocalization. We thus show that PC and centrosome act as a single signaling unit, linked by ciliary cAMP diffusion regulating the rhythmicity of saltatory migration at the centrosome. We generalized this finding to embryonic and adult migrating neurons.