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Nat Cell Biol. 2014 Feb;16(2):133-44. doi: 10.1038/ncb2906. Epub 2014 Jan 26.

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

Author information

1
1] 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.
2
Department of Chemical and Systems Biology, Stanford University School of MedicineStanford California 94305 USA.

Abstract

Ca(2+) signals control cell migration by regulating forward movement and cell adhesion. However, it is not well understood how Ca(2+)-regulatory proteins and second messengers are spatially organized in migrating cells. Here we show that receptor tyrosine kinase and phospholipase C signalling are restricted to the front of migrating endothelial leader cells, triggering local Ca(2+) pulses, local depletion of Ca(2+) in the endoplasmic reticulum and local activation of STIM1, supporting pulsatile front retraction and adhesion. At the same time, the mediator of store-operated Ca(2+) influx, STIM1, is transported by microtubule plus ends to the front. Furthermore, higher Ca(2+) pump rates in the front relative to the back of the plasma membrane enable effective local Ca(2+) signalling by locally decreasing basal Ca(2+). Finally, polarized phospholipase C signalling generates a diacylglycerol gradient towards the front that promotes persistent forward migration. Thus, cells employ an integrated Ca(2+) control system with polarized Ca(2+) signalling proteins and second messengers to synergistically promote directed cell migration.

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PMID:
24463606
PMCID:
PMC3953390
DOI:
10.1038/ncb2906
[Indexed for MEDLINE]
Free PMC Article
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