Regulation of cell movement is mediated by stretch-activated calcium channels

Intracellular calcium regulates many of the molecular processes that are essential for cell movement1. It is required for the production of actomyosin-based contractile forces2,3,4, the regulation of the structure and dynamics of the actin cytoskeleton5,6, and the formation and disassembly of cell–substratum adhesions7,8. Calcium also serves as a second messenger in many biochemical signal-transduction pathways7. However, despite the pivotal role of calcium in motile processes, it is not clear how calcium regulates overall cell movement. Here we show that transient increases in intracellular calcium, [Ca2+]i, during the locomotion of fish epithelial keratocytes, occur more frequently in cells that become temporarily ‘stuck’ to the substratum or when subjected to mechanical stretching. We find that calcium transients arise from the activation of stretch-activated calcium channels, which triggers an influx of extracellular calcium. In addition, the subsequent increase in [Ca2+]i is involved in detachment of the rear cell margin. Thus, we have defined a mechanism by which cells can detect and transduce mechanical forces into biochemical signals that can modulate locomotion.