Ca2+ Pulses Control Local Cycles of Lamellipodia Retraction and Adhesion along the Front of Migrating Cells
Open accessAbstract
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.
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Local changes in intracellular calcium play a critical role in regulating cell migration and chemotaxis in diverse cell types.
“Local changes in intracellular calcium play a critical role in regulating cell migration and chemotaxis in diverse cell types48–50.”
From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [50]
The Results and Discussion (page not available) show that local Ca2+ pulses regulate retraction and adhesion in migrating human endothelial cells and suggest a role in migration and chemotaxis. The paper cites evidence concerning other cell types, but its own finding is limited to endothelial cells; it does not establish that local calcium changes play a critical role in chemotaxis across diverse cell types. (LLM, conf=0.85)
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Research works printed but not linked: 23
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Obst, J., Hall-Roberts, H. L., Smith, T. B., Kreuzer, M., Magno, L., Di Daniel, E., Davis, J. B., & Mead, E. (2021) · Scientific Reports · doi:10.1038/s41598-021-96144-7 · Cited by 36 · see citing works
- Authors
- Tsai, F.-C., & Meyer, T.
- Affiliations
- Stanford University (US)
- Corresponding author
- Meyer, Tobias
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 22
- Issue
- 9
- Pages
- 837-842
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3503311
- OpenAlex
- W1974114145
- Cited by
- 141
- References
- 0
- Citations by year
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- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM063702, R01GM030179)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- calcium signaling, focal adhesions, cell migration, endothelial cells, myosin II, myosin light chain kinase, paxillin, leading edge, chemotaxis
- MeSH terms
- Calcium, Cell Adhesion, Cell Movement
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