Calcium flickers steer cell migration.
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.
Wei
Chaoliang
C
Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China. chaoliang.wei@gmail.com
Wang
Xianhua
X
Chen
Min
M
Ouyang
Kunfu
K
Song
Long-Sheng
LS
Cheng
Heping
H
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D050053:TRPM Cation Channels; D019284:Thapsigargin; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium