期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：21
页码：5952-5957
DOI：10.1073/pnas.1518412113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
