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.