Epidermal keratinocyte polarity and motility require Ca²⁺ influx through TRPV1.
Ca(2+) has long been known to play an important role in cellular polarity and guidance. We studied the role of Ca(2+) signaling during random and directed cell migration to better understand whether Ca(2+) 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 Ca(2+) (Ca(2+)i) during migration and automated image alignment enabled us to characterize and map the spatiotemporal changes in Ca(2+)i. We show that asymmetric distributions of lamellipodial Ca(2+) sparks are encoded in frequency, not amplitude, and that they correlate with cellular rotation during migration. Directed migration during galvanotaxis increases the frequency of Ca(2+) sparks over the entire lamellipod; however, these events do not give rise to asymmetric Ca(2+)i signals that correlate with turning. We demonstrate that Ca(2+)-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(2+)i activity are affected by pharmacological agents that target TRPV1, indicating a novel role for this channel during cell migration.
Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
David M
DM
Graham
Ling
L
Huang
Kenneth R
KR
Robinson
Mark A
MA
Messerli
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
D050916:TRPV Cation Channels; C581231:TRPV1 protein, zebrafish; D029961:Zebrafish Proteins; D002118:Calcium
Ca2+; Motility; Polarity; Skin; TRPV1