Flickering calcium microdomains signal turning of migrating cells

It has been well-established that polarized migrating cells exhibit a stable and transient gradient of intracellular calcium concentration ([Ca2+]i), increasing from front-to-rear, that is thought to be responsible for rear retraction. The paradox that arises is how calcium at the front of a cell catalyzes critical high-threshold calcium-dependent processes during cell migration and particularly in decision-making for a cell to turn. In this brief review, we discuss the recent discovery of flickering high-[Ca2+]i microdomains ("calcium flickers") at the front of migrating fibroblasts and their common role in transducing local membrane mechanical stress (via TRPM7, a stretch-activated calcium-permeating transient receptor potential channel) and chemoattractant-elicited signals (via type 2 inositol 1,4,5-trisphosphate receptor in the endoplasmic reticulum). Furthermore, we present a new model for patterned calcium flicker activity as the mechanism for steering the turning of a migrating cell.