Optogenetic toolkit reveals the role of Ca2+ sparklets in coordinated cell migration

Abstract

Cell migration is controlled by various Ca2+ signals. Local Ca2+ signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca2+ signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca2+ signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca2+ sparklets mediated by L-type voltage-dependent Ca2+ channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca2+ influx acts as an essential transducer in establishing a global front-to-rear increasing Ca2+ gradient. This asymmetrical Ca2+ gradient is crucial for maintaining front-rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca2+ sparklets and front-rear coordination during directed cell migration.