CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration

Abstract Directed cell migration requires sustained cell polarisation. In migrating cortical interneurons, nuclear movements are directed towards the centrosome that organises the primary cilium signalling hub. Primary cilium-elicited signalling, and how it affects migration, remain however ill char...

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Main Authors: Melody Atkins, Maud Wurmser, Michèle Darmon, Fiona Roche, Xavier Nicol, Christine Métin
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43645-w
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author Melody Atkins
Maud Wurmser
Michèle Darmon
Fiona Roche
Xavier Nicol
Christine Métin
author_facet Melody Atkins
Maud Wurmser
Michèle Darmon
Fiona Roche
Xavier Nicol
Christine Métin
author_sort Melody Atkins
collection DOAJ
description Abstract Directed cell migration requires sustained cell polarisation. In migrating cortical interneurons, nuclear movements are directed towards the centrosome that organises the primary cilium signalling hub. Primary cilium-elicited signalling, and how it affects migration, remain however ill characterised. Here, we show that altering cAMP/cGMP levels in the primary cilium by buffering cAMP, cGMP or by locally increasing cAMP, influences the polarity and directionality of migrating interneurons, whereas buffering cAMP or cGMP in the apposed centrosome compartment alters their motility. Remarkably, we identify CXCL12 as a trigger that targets the ciliary cAMP/cGMP ratio to promote sustained polarity and directed migration. We thereby uncover cAMP/cGMP levels in the primary cilium as a major target of extrinsic cues and as the steering wheel of neuronal migration.
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spelling doaj.art-48008bb414874d9989f5a4ece69697e52023-12-10T12:24:51ZengNature PortfolioNature Communications2041-17232023-12-0114111710.1038/s41467-023-43645-wCXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migrationMelody Atkins0Maud Wurmser1Michèle Darmon2Fiona Roche3Xavier Nicol4Christine Métin5INSERM UMR-S 1270; Institut du Fer à Moulin, Sorbonne UniversitéInstitut de la Vision, Sorbonne Université, INSERM CNRSINSERM UMR-S 1270; Institut du Fer à Moulin, Sorbonne UniversitéInstitut de la Vision, Sorbonne Université, INSERM CNRSInstitut de la Vision, Sorbonne Université, INSERM CNRSINSERM UMR-S 1270; Institut du Fer à Moulin, Sorbonne UniversitéAbstract Directed cell migration requires sustained cell polarisation. In migrating cortical interneurons, nuclear movements are directed towards the centrosome that organises the primary cilium signalling hub. Primary cilium-elicited signalling, and how it affects migration, remain however ill characterised. Here, we show that altering cAMP/cGMP levels in the primary cilium by buffering cAMP, cGMP or by locally increasing cAMP, influences the polarity and directionality of migrating interneurons, whereas buffering cAMP or cGMP in the apposed centrosome compartment alters their motility. Remarkably, we identify CXCL12 as a trigger that targets the ciliary cAMP/cGMP ratio to promote sustained polarity and directed migration. We thereby uncover cAMP/cGMP levels in the primary cilium as a major target of extrinsic cues and as the steering wheel of neuronal migration.https://doi.org/10.1038/s41467-023-43645-w
spellingShingle Melody Atkins
Maud Wurmser
Michèle Darmon
Fiona Roche
Xavier Nicol
Christine Métin
CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Nature Communications
title CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
title_full CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
title_fullStr CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
title_full_unstemmed CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
title_short CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
title_sort cxcl12 targets the primary cilium camp cgmp ratio to regulate cell polarity during migration
url https://doi.org/10.1038/s41467-023-43645-w
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