title: Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1.
abstract: Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP₃ receptors (IP₃Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP₃R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP₃R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP₃R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment.
authors: Inserm-U932 Institut Curie, Paris, France.
authors: Paola
authors: P
authors: Solanes
authors: Inserm-U932 Institut Curie, Paris, France.
authors: Mélina L
authors: ML
authors: Heuzé
authors: Inserm-U932 Institut Curie, Paris, France.
authors: Mathieu
authors: M
authors: Maurin
authors: Inserm-U932 Institut Curie, Paris, France.
authors: Marine
authors: M
authors: Bretou
authors: CNRS-UMR144 Institut Curie, Paris, France.
authors: Franziska
authors: F
authors: Lautenschlaeger
authors: CNRS-UMR144 Institut Curie, Paris, France.
authors: Paolo
authors: P
authors: Maiuri
authors: CNRS-UMR144 Institut Curie, Paris, France.
authors: Emmanuel
authors: E
authors: Terriac
authors: Unité de Virologie Structurale, CNRS-UMR3469 Institut Pasteur, Paris, France.
authors: Maria-Isabel
authors: MI
authors: Thoulouze
authors: Faculté de Médecine X. Bichat, Inserm-U1149, Paris, France.
authors: Pierre
authors: P
authors: Launay
authors: CNRS-UMR144 Institut Curie, Paris, France.
authors: Matthieu
authors: M
authors: Piel
authors: Inserm-U932 Institut Curie, Paris, France pablo.vargas@curie.fr amlennon@curie.fr.
authors: Pablo
authors: P
authors: Vargas
authors: Inserm-U932 Institut Curie, Paris, France pablo.vargas@curie.fr amlennon@curie.fr.
authors: Ana-Maria
authors: AM
authors: Lennon-Duménil
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology*; D005434:Flow Cytometry; D015151:Immunoblotting; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D024462:Myosin Type II / Q000378:metabolism*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D024462:Myosin Type II; D002118:Calcium
keywords: IP3 receptors; calcium; cell migration; dendritic cells; myosin II
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