Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions.
J. Biol. Chem.. 2004-04-21; 279(27): 28715-28723
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1. J Biol Chem. 2004 Jul 2;279(27):28715-23. Epub 2004 Apr 21.
Calcium rises locally trigger focal adhesion disassembly and enhance residency of
focal adhesion kinase at focal adhesions.
Giannone G(1), Rondé P, Gaire M, Beaudouin J, Haiech J, Ellenberg J, Takeda K.
(1)Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et
Moléculaires, Unité Mixte de Recherche CNRS 7034, Université Louis Pasteur de
Strasbourg, 67401 Illkirch, France.
Focal adhesion kinase (FAK) activity and Ca(2+) signaling led to a turnover of
focal adhesions (FAs) required for cell spreading and migration. We used yellow
Cameleon-2 (Ycam), a fluorescent protein-based Ca(2+) sensor fused to FAK or to a
FAK-related non-kinase domain, to measure simultaneously local Ca(2+) variations
at FA sites and FA dynamics. Discrete subcellular Ca(2+) oscillators initiate
both propagating and abortive Ca(2+) waves in migrating U87 astrocytoma cells.
Ca(2+)-dependent FA disassembly occurs when the Ca(2+) wave reaches individual
FAs, indicating that local but not global Ca(2+) increases trigger FA
disassembly. An unexpectedly rapid flux of FAK between cytosolic and FA
compartments was revealed by fluorescence recovery after photobleaching studies.
The FAK-Ycam recovery half-time (17 s) at FAs was slowed (to 29 s) by Ca(2+)
elevation. FAK-related non-kinase domain-Ycam had a faster, Ca(2+)-insensitive
recovery half-time (11 s), which is consistent with the effect of Ca(2+) on
FAK-Ycam dynamics not being due to a general modification of the dynamics of FA
components. Because FAK association at FAs was prolonged by Ca(2+) and FAK
autophosphorylation was correlated to intracellular Ca(2+) levels, we propose
that local Ca(2+) elevations increase the residency of FAK at FAs, possibly by
means of tyrosine phosphorylation of FAK, thereby leading to increased activation
of its effectors involved in FA disassembly.
PMID: 15102844 [Indexed for MEDLINE]