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

Julie Stoufflet, Maxime Chaulet, Mohamed Doulazmi, Coralie Fouquet, Caroline Dubacq, Christine Métin, Alain Trembleau, Pierre Vincent, Isabelle Caillé
doi: https://doi.org/10.1101/765925
Julie Stoufflet
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
2Sorbonne Université, CNRS UMR8256, Institut Biologie Paris Seine (IBPS), Biological adaptation and ageing (B2A), F-75005 Paris, France
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Maxime Chaulet
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
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Mohamed Doulazmi
2Sorbonne Université, CNRS UMR8256, Institut Biologie Paris Seine (IBPS), Biological adaptation and ageing (B2A), F-75005 Paris, France
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Coralie Fouquet
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
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Caroline Dubacq
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
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Christine Métin
3Inserm UMR-S839. Institut du Fer à Moulin, Sorbonne Université, Paris, France
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Alain Trembleau
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
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Pierre Vincent
2Sorbonne Université, CNRS UMR8256, Institut Biologie Paris Seine (IBPS), Biological adaptation and ageing (B2A), F-75005 Paris, France
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  • For correspondence: isabelle.caille@upmc.fr pierre.vincent@upmc.fr
Isabelle Caillé
1Sorbonne Université, CNRS UMR8246, Inserm U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), F-75005 Paris, France
4Université de Paris, Paris, France
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  • For correspondence: isabelle.caille@upmc.fr pierre.vincent@upmc.fr
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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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Posted November 12, 2019.
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Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration
Julie Stoufflet, Maxime Chaulet, Mohamed Doulazmi, Coralie Fouquet, Caroline Dubacq, Christine Métin, Alain Trembleau, Pierre Vincent, Isabelle Caillé
bioRxiv 765925; doi: https://doi.org/10.1101/765925
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Primary cilium-dependent cAMP/PKA signaling at the centrosome regulates neuronal migration
Julie Stoufflet, Maxime Chaulet, Mohamed Doulazmi, Coralie Fouquet, Caroline Dubacq, Christine Métin, Alain Trembleau, Pierre Vincent, Isabelle Caillé
bioRxiv 765925; doi: https://doi.org/10.1101/765925

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