title: Ca2+ pulses control local cycles of lamellipodia retraction and adhesion along the front of migrating cells.
abstract: Ca(2+) signals regulate polarization, speed, and turning of migrating cells. However, the molecular mechanism by which Ca(2+) acts on moving cells is not understood. Here we show that local Ca(2+) pulses along the front of migrating human endothelial cells trigger cycles of retraction of local lamellipodia and, concomitantly, strengthen local adhesion to the extracellular matrix. These Ca(2+) release pulses had small amplitudes and diameters and were triggered repetitively near the leading plasma membrane with only little coordination between different regions. We show that each Ca(2+) pulse triggers contraction of actin filaments by activating myosin light-chain kinase and myosin II behind the leading edge. The cyclic force generated by myosin II operates locally, causing a partial retraction of the nearby protruding lamellipodia membrane and a strengthening of paxillin-based focal adhesion within the same lamellipodia. Photo release of Ca(2+) demonstrated a direct role of Ca(2+) in triggering local retraction and adhesion. Together, our study suggests that spatial sensing, forward movement, turning, and chemotaxis are in part controlled by confined Ca(2+) pulses that promote local lamellipodia retraction and adhesion cycles along the leading edge of moving cells.
authors.affiliation: Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Feng-Chiao
authors.initials: FC
authors.lastname: Tsai
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement
chemical_list: D002118:Calcium