Calcium flickers steer cell migration

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Abstract
Directional cell movement depends on an intracellular calcium gradient. In a study of migrating fibroblasts, Chaoliang Wei et al. have identified calcium flickers — high-calcium microdomains — as part of the mechanism that steers cells to their targets. The flickers are most active at the leading edge of migrating cells. In the presence of a chemotactic gradient, an asymmetric gradient of calcium flicker activity develops which promotes turning of cells towards the direction of the chemoattractant. Directional cell movement depends on an intracellular calcium gradient. This study identifies calcium flickers in migrating fibroblasts and these are most active at the leading edge of cells. In the presence of a chemotactic gradient, an asymmetric gradient of calcium flicker activity develops which promotes turning of cells towards the direction of the chemoattractant. Directional movement is a property common to all cell types during development and is critical to tissue remodelling and regeneration after damage1,2,3. In migrating cells, calcium has a multifunctional role in directional sensing, cytoskeleton redistribution, traction force generation, and relocation of focal adhesions1,4,5,6,7. Here we visualize high-calcium microdomains (‘calcium flickers’) and their patterned activation in migrating human embryonic lung fibroblasts. Calcium flicker activity is dually coupled to membrane tension (by means of TRPM7, a stretch-activated Ca2+-permeant channel of the transient receptor potential superfamily8) and chemoattractant signal transduction (by means of type 2 inositol-1,4,5-trisphosphate receptors). Interestingly, calcium flickers are most active at the leading lamella of migrating cells, displaying a 4:1 front-to-rear polarization opposite to the global calcium gradient6. When exposed to a platelet-derived growth factor gradient perpendicular to cell movement, asymmetric calcium flicker activity develops across the lamella and promotes the turning of migrating fibroblasts. These findings show how the exquisite spatiotemporal organization of calcium microdomains can orchestrate complex cellular processes such as cell migration.