PMID- 25637353 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20181113 IS - 1460-2075 (Electronic) IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 34 IP - 6 DP - 2015 Mar 12 TI - Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1. PG - 798-810 LID - 10.15252/embj.201489056 [doi] AB - 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. IP(3) receptors (IP(3)Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP(3)R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP(3)R1 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 IP(3)R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. CI - (c) 2015 Institut Curie/Inserm. Published under the terms of the CC BY NC ND 4.0 license. FAU - Solanes, Paola AU - Solanes P AD - Inserm-U932 Institut Curie, Paris, France. FAU - Heuze, Melina L AU - Heuze ML AD - Inserm-U932 Institut Curie, Paris, France. FAU - Maurin, Mathieu AU - Maurin M AD - Inserm-U932 Institut Curie, Paris, France. FAU - Bretou, Marine AU - Bretou M AD - Inserm-U932 Institut Curie, Paris, France. FAU - Lautenschlaeger, Franziska AU - Lautenschlaeger F AD - CNRS-UMR144 Institut Curie, Paris, France. FAU - Maiuri, Paolo AU - Maiuri P AD - CNRS-UMR144 Institut Curie, Paris, France. FAU - Terriac, Emmanuel AU - Terriac E AD - CNRS-UMR144 Institut Curie, Paris, France. FAU - Thoulouze, Maria-Isabel AU - Thoulouze MI AD - Unite de Virologie Structurale, CNRS-UMR3469 Institut Pasteur, Paris, France. FAU - Launay, Pierre AU - Launay P AD - Faculte de Medecine X. Bichat, Inserm-U1149, Paris, France. FAU - Piel, Matthieu AU - Piel M AD - CNRS-UMR144 Institut Curie, Paris, France. FAU - Vargas, Pablo AU - Vargas P AD - Inserm-U932 Institut Curie, Paris, France pablo.vargas@curie.fr amlennon@curie.fr. FAU - Lennon-Dumenil, Ana-Maria AU - Lennon-Dumenil AM AD - Inserm-U932 Institut Curie, Paris, France pablo.vargas@curie.fr amlennon@curie.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150130 PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (DNA Primers) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - EC 3.6.1.- (Myosin Type II) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Cell Movement/*physiology MH - Cell Polarity MH - DNA Primers/genetics MH - Dendritic Cells/*immunology MH - Endoplasmic Reticulum/metabolism MH - Extracellular Space/*immunology MH - Flow Cytometry MH - Immunoblotting MH - Inositol 1,4,5-Trisphosphate Receptors/*metabolism MH - Mice MH - Microscopy, Fluorescence MH - Microscopy, Video MH - Myosin Type II/*metabolism MH - Phosphorylation MH - Real-Time Polymerase Chain Reaction PMC - PMC4369315 OTO - NOTNLM OT - IP3 receptors OT - calcium OT - cell migration OT - dendritic cells OT - myosin II EDAT- 2015/02/01 06:00 MHDA- 2015/05/12 06:00 PMCR- 2016/03/12 CRDT- 2015/02/01 06:00 PHST- 2015/02/01 06:00 [entrez] PHST- 2015/02/01 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] PHST- 2016/03/12 00:00 [pmc-release] AID - embj.201489056 [pii] AID - 10.15252/embj.201489056 [doi] PST - ppublish SO - EMBO J. 2015 Mar 12;34(6):798-810. doi: 10.15252/embj.201489056. Epub 2015 Jan 30.