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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Format: | Article |
Language: | English |
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Nature Portfolio
2023-12-01
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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. |
first_indexed | 2024-03-09T01:16:28Z |
format | Article |
id | doaj.art-48008bb414874d9989f5a4ece69697e5 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-09T01:16:28Z |
publishDate | 2023-12-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
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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