Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1

Abstract

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 using primary zebrafish keratinocytes. Rapid linescan and time lapse imaging of Ca2+i during migration and automated image alignment enabled us to characterize and map the spatiotemporal changes in Ca2+i. We show that asymmetric distributions of lamellipodial Ca2+ sparks are encoded in frequency, not amplitude, and 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 Ca2+i 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. Lastly, we demonstrate that cell motility and Ca2+i activity are affected by TRPV1 pharmacological agents, indicating a novel role for this channel during cell migration.