Calcium flickers steer cell migration

Nature. 2009 Feb 12;457(7231):901-5. doi: 10.1038/nature07577. Epub 2008 Dec 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Cell Line
  • Cell Polarity / physiology
  • Chemotaxis / drug effects
  • Chemotaxis / physiology*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Gene Expression Regulation, Developmental
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Protein-Serine-Threonine Kinases
  • TRPM Cation Channels / metabolism
  • Thapsigargin / pharmacology


  • Enzyme Inhibitors
  • Inositol 1,4,5-Trisphosphate Receptors
  • TRPM Cation Channels
  • Thapsigargin
  • Protein-Serine-Threonine Kinases
  • TRPM7 protein, human
  • Calcium-Transporting ATPases
  • Calcium