Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1
Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1
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DOI：
10.1242/jcs.122192
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发表时间：
2013-10-15
影响因子：
4
通讯作者：
Messerli, Mark A.
中科院分区：
文献类型：
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作者：
Graham, David M.;Huang, Ling;Messerli, Mark A.
长期以来，人们一直认为Ca 2+在细胞极性和指导中起着重要作用。我们研究了随机和定向细胞迁移过程中Ca 2+信号的作用，以更好地了解Ca 2+是否从前沿指导细胞运动，以及使用原代斑马鱼角质形成细胞参与此功能的离子通道。在迁移和自动图像对齐期间细胞内Ca 2+（Ca 1（2+））的快速线扫描和延时成像使我们能够表征和绘制Ca 1（2+）的时空变化。我们发现，不对称分布的层状lipodial钙火花编码的频率，而不是振幅，它们与细胞旋转迁移过程中。趋电过程中的定向迁移增加了整个片足动物的Ca 2+火花频率;然而，这些事件不会引起与转向相关的不对称Ca-1（2+）信号。我们证明，这些细胞内的Ca 2+渗透性通道是机械激活的，包括几个瞬时受体电位家族成员，包括TRPV 1。最后，我们证明了细胞运动性和Ca-i（2+）活性受到靶向TRPV 1的药理学药物的影响，表明该通道在细胞迁移过程中的新作用。
Ca2+ has long been known to play an important role in cellular polarity and guidance. We studied the role of Ca2+ signaling during random and directed cell migration to better understand whether Ca2+ directs cell motility from the leading edge and which ion channels are involved in this function by using primary zebrafish keratinocytes. Rapid line-scan and time-lapse imaging of intracellular Ca2+ (Ca-i(2+)) during migration and automated image alignment enabled us to characterize and map the spatiotemporal changes in Ca-i(2+). We show that asymmetric distributions of lamellipodial Ca2+ sparks are encoded in frequency, not amplitude, and that they correlate with cellular rotation during migration. Directed migration during galvanotaxis increases the frequency of Ca2+ sparks over the entire lamellipod; however, these events do not give rise to asymmetric Ca-i(2+) signals that correlate with turning. We demonstrate that Ca2+-permeable channels within these cells are mechanically activated and include several transient receptor potential family members, including TRPV1. Last, we demonstrate that cell motility and Ca-i(2+) activity are affected by pharmacological agents that target TRPV1, indicating a novel role for this channel during cell migration.