title: Optogenetic toolkit reveals the role of Ca2+ sparklets in coordinated cell migration.
abstract: Cell migration is controlled by various Ca(2+) signals. Local Ca(2+) signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca(2+) signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca(2+) signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca(2+) sparklets mediated by L-type voltage-dependent Ca(2+) channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca(2+) influx acts as an essential transducer in establishing a global front-to-rear increasing Ca(2+) gradient. This asymmetrical Ca(2+) 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 Ca(2+) sparklets and front-rear coordination during directed cell migration.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 03080, Republic of Korea;
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea;
authors.forename: Minji
authors.initials: M
authors.lastname: Lee
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34141, Republic of Korea;
authors.forename: Nury
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34141, Republic of Korea; KAIST Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea wdheo@kaist.ac.kr.
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D062308:Optogenetics / Q000379:methods*
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium
keywords: actin cytoskeleton; calcium signaling; cell migration; cell polarity; optogenetics