한빛사 논문
Abstract
Jin Man Kima,b,1, Minji Leec,1, Nury Kimd, and Won Do Heoc,d,e,2
aGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea;
bDepartment of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 03080, Republic of Korea;
cDepartment of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea;
dCenter for Cognition and Sociality, Institute for Basic Science, Daejeon 34141, Republic of Korea;
eKAIST Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea
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.
optogenetics, cell migration, calcium signaling, cell polarity, actin cytoskeleton
1J.M.K. and M.L. contributed equally to this work.
2To whom correspondence should be addressed.
Author contributions: J.M.K., M.L., N.K., and W.D.H. designed research; J.M.K. and M.L. performed research; J.M.K. contributed new reagents/analytic tools; J.M.K., M.L., N.K., and W.D.H. analyzed data; and J.M.K., M.L., N.K., and W.D.H. wrote the paper
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