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Curr Biol. 2012 May 8;22(9):837-42. doi: 10.1016/j.cub.2012.03.037. Epub 2012 Apr 19.

Ca2+ pulses control local cycles of lamellipodia retraction and adhesion along the front of migrating cells.

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1
Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.

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.

PMID:
22521790
PMCID:
PMC3503311
DOI:
10.1016/j.cub.2012.03.037
[Indexed for MEDLINE]
Free PMC Article
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