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bioRxiv · 10.1101/765925

Primary cilium cAMP regulates cyclic saltatory neuronal migration at the centrosome

Stoufflet, J.·Chaulet, M.·Doulazmi, M.·Fouquet, C.·Dubacq, C.·Metin, C.·Trembleau, A.·Vincent, P.·Caille, I.
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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 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

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Stoufflet, J., Chaulet, M., Doulazmi, M., Fouquet, C., Dubacq, C., Metin, C., Trembleau, A., Vincent, P., Caille, I.. 2019-09-13. Primary cilium cAMP regulates cyclic saltatory neuronal migration at the centrosome. https://doi.org/10.1101/765925

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