Calcium oscillations trigger focal adhesion disassembly in human U87 astrocytoma cells.
J. Biol. Chem.. 2002-05-14; 277(29): 26364-26371
DOI: 10.1074/jbc.m203952200
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1. J Biol Chem. 2002 Jul 19;277(29):26364-71. Epub 2002 May 14.
Calcium oscillations trigger focal adhesion disassembly in human U87 astrocytoma
cells.
Giannone G(1), Rondé P, Gaire M, Haiech J, Takeda K.
Author information:
(1)Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et
Moléculaires, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, 67401
Illkirch, France.
Integrin-associated intracellular Ca(2+) oscillations modulate cell migration,
probably by controlling integrin-mediated release of the cell rear during
migration. Focal adhesion kinase (FAK), via its tyrosine phosphorylation
activity, plays a key role in integrin signaling. In human U87 astrocytoma cells,
expression of the dominant negative FAK-related non-kinase domain (FRNK) inhibits
the Ca(2+)-sensitive component of serum-dependent migration. We investigated how
integrin-associated Ca(2+) signaling might be coupled to focal adhesion (FA)
dynamics by visualizing the effects of Ca(2+) spikes on FAs using green
fluorescent protein (GFP)-tagged FAK and FRNK. We report that Ca(2+) spikes are
temporally correlated with movement and disassembly of FAs, but not their
formation. FRNK transfection did not affect generation of Ca(2+) spikes, although
cell morphology was altered, with fewer FAs of larger size and having a more
peripheral localization being observed. Larger sized FAs in FRNK-transfected
cells were not disassembled by Ca(2+) spikes, providing a possible explanation
for impaired Ca(2+)-dependent migration in these cells. Stress fiber end
movements initiated by Ca(2+) spikes were visualized using GFP-tagged myosin
light chain kinase (MLCK). Ca(2+)-associated movements of stress fiber ends and
FAs had similar kinetics, suggesting that stress fibers and FAs move in a
coordinated fashion. This indicates that increases in Ca(2+) likely trigger
disassembly of adhesive structures that involves disruption of
integrin-extracellular matrix interactions, supporting a key role for
Ca(2+)-sensitive inside-out signaling in cell migration. A rapid increase in
tyrosine phosphorylation of FAK was found in response to an elevation in Ca(2+)
induced by thapsigargin, and we propose that this represents the initial
triggering event linking Ca(2+) signaling and FA dynamics to cell motility.
DOI: 10.1074/jbc.M203952200
PMID: 12011063 [Indexed for MEDLINE]