Abstract
Cell adhesion is crucial for migration of cells during development, and cell–substrate adhesion of motile cells is accomplished through the formation and removal of focal complexes that are sites of cell–substrate contact. Because Ca 2+ signaling regulates the rate of axon outgrowth and growth cone turning, we investigated the potential role of Ca 2+ in focal complex dynamics. We describe a novel class of localized, spontaneous transient elevations of cytosolic Ca 2+ observed both in Xenopus neuronal growth cones and fibroblasts that are 2–6 μm in spatial extent and 2–4 s in duration. They are distributed throughout growth cone lamellipodia and at the periphery of fibroblast pseudopodia, which are regions of high motility. In both cell types, these Ca 2+ transients lead to disappearance of phosphorylated focal adhesion kinase (pFAK) and deadhesion from the substrate as assessed by confocal and internal reflection microscopy, respectively. The loss of pFAK is inhibited by cyclosporin A, suggesting that these Ca 2+ transients exert their effects via calcineurin. These results identify an intrinsic mechanism for local cell detachment that may be modulated by agents that regulate motility.
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