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

Melody Atkins (), Maud Wurmser, Michèle Darmon, Fiona Roche, Xavier Nicol and Christine Métin ()
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Melody Atkins: Sorbonne Université
Maud Wurmser: Sorbonne Université, INSERM CNRS
Michèle Darmon: Sorbonne Université
Fiona Roche: Sorbonne Université, INSERM CNRS
Xavier Nicol: Sorbonne Université, INSERM CNRS
Christine Métin: Sorbonne Université

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43645-w

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