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A polarized Ca2+, diacylglycerol and STIM1 signalling system regulates directed cell migration

Feng-Chiao Tsai1, Akiko Seki2, Hee Won Yang2

  • 11] Program of Cancer Biology, Stanford University School of MedicineStanford California 94305 USA [2] Department of Chemical and Systems Biology, Stanford University School of MedicineStanford California 94305 USA [3] Institute of Molecular Medicine, National Taiwan University College of MedicineTaipei 100 Taiwan.

Nature Cell Biology
|January 28, 2014
PubMed

Insights

Calcium (Ca2+) signals guide cell migration. This study reveals polarized signaling proteins and localized Ca2+ pulses at the cell front drive directed endothelial cell movement and adhesion.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Cell migration is crucial for development and disease.
  • Calcium (Ca2+) signaling regulates cell movement and adhesion.
  • Spatial organization of Ca2+ signaling components in migrating cells remains unclear.

Purpose of the Study:

  • To elucidate the spatial organization of Ca2+ signaling in migrating endothelial cells.
  • To understand how localized Ca2+ signals control cell front dynamics and adhesion.
  • To investigate the role of polarized signaling in directed cell migration.

Main Methods:

  • Confocal microscopy to visualize Ca2+ signals and protein localization.
  • Pharmacological inhibition of signaling pathways.
  • Live-cell imaging of endothelial leader cells.
  • Analysis of STIM1 transport and Ca2+ pump activity.

Main Results:

  • Receptor tyrosine kinase and phospholipase C signaling are front-restricted, inducing local Ca2+ pulses and STIM1 activation.
  • STIM1 is transported to the cell front via microtubule plus ends.
  • Polarized Ca2+ pump activity and diacylglycerol gradients enhance forward migration.
  • Integrated Ca2+ control system promotes directed cell migration.

Conclusions:

  • Directed cell migration relies on a spatially organized Ca2+ signaling network.
  • Polarized signaling proteins and localized Ca2+ dynamics are essential for cell front retraction and adhesion.
  • This integrated system ensures persistent and directed endothelial cell movement.

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