Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1

作者：Solanes Paola; Heuze Melina L; Maurin Mathieu; Bretou Marine; Lautenschlaeger Franziska; Maiuri Paolo; Terriac Emmanuel; Thoulouze Maria Isabel; Launay Pierre; Piel Matthieu; Vargas Pablo^*; Lennon Dumenil Ana Maria

来源：The EMBO Journal, 2015, 34(6): 798-810.

DOI：10.15252/embj.201489056

• calcium
• cell migration
• dendritic cells
• IP3 receptors
• myosin II

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 (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.

• 出版日期2015-3-12