Calcium flickers steer cell migration
Open accessAbstract
Directional movement is a property common to all cell types during development and is critical to tissue remodelling and regeneration after damage. In migrating cells, calcium has a multifunctional role in directional sensing, cytoskeleton redistribution, traction force generation, and relocation of focal adhesions. Here we visualize high-calcium microdomains ('calcium flickers') and their patterned activation in migrating human embryonic lung fibroblasts. Calcium flicker activity is dually coupled to membrane tension (by means of TRPM7, a stretch-activated Ca(2+)-permeant channel of the transient receptor potential superfamily) and chemoattractant signal transduction (by means of type 2 inositol-1,4,5-trisphosphate receptors). Interestingly, calcium flickers are most active at the leading lamella of migrating cells, displaying a 4:1 front-to-rear polarization opposite to the global calcium gradient. When exposed to a platelet-derived growth factor gradient perpendicular to cell movement, asymmetric calcium flicker activity develops across the lamella and promotes the turning of migrating fibroblasts. These findings show how the exquisite spatiotemporal organization of calcium microdomains can orchestrate complex cellular processes such as cell migration.
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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 [48]
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Self-citation
- Authors
- Wei, C., Wang, X., Chen, M., Ouyang, K., Song, L.-S., & Cheng, H.
- Affiliations
- Peking University (CN)
- University of Iowa (US)
- Corresponding author
- Wei, Chaoliang
- Cheng, Heping
- Venue
- Nature
- Published
- 2009-02-01
- Volume
- 457
- Issue
- 7231
- Pages
- 901-905
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3505761
- OpenAlex
- W2081848364
- Cited by
- 611
- References
- 0
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 20 · 2023: 27 · 2022: 37 · 2021: 45 · 2020: 40 · 2019: 28 · 2018: 30 · 2017: 48 · 2016: 35 · 2015: 32 · 2014: 57 · 2013: 51 · 2012: 38
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL090905, HL090905)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- directional cell migration, fibroblast chemotaxis, TRPM7, IP3 receptor, membrane tension, calcium gradient, platelet-derived growth factor, chemoattractant signaling, human embryonic lung fibroblasts
- MeSH terms
- Calcium-Transporting ATPases, Calcium, Cell Line, Chemotaxis, Endoplasmic Reticulum, Enzyme Inhibitors, Fibroblasts, Humans, Cell Polarity, Protein Serine-Threonine Kinases, Gene Expression Regulation, Developmental, Thapsigargin, TRPM Cation Channels, Inositol 1,4,5-Trisphosphate Receptors
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