RT Journal Article
SR Electronic
T1 Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 765925
DO 10.1101/765925
A1 Stoufflet, Julie
A1 Chaulet, Maxime
A1 Doulazmi, Mohamed
A1 Fouquet, Coralie
A1 Dubacq, Caroline
A1 Métin, Christine
A1 Trembleau, Alain
A1 Vincent, Pierre
A1 Caillé, Isabelle
YR 2019
UL http://biorxiv.org/content/early/2019/11/12/765925.abstract
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