Coronin 2A regulates a subset of focal-adhesion-turnover events through the cofilin pathway.
Coronins are conserved F-actin-binding proteins that are important for motility and actin dynamics. Unlike type I coronins, coronin 2A localizes to stress fibers and some focal adhesions, and is excluded from the leading edge. Depletion of coronin 2A in MTLn3 cells decreases cell motility and turnover of focal adhesions. Surprisingly, none of the pathways known to regulate focal-adhesion turnover are affected by depletion of coronin 2A. Depletion of coronin 2A does, however, increase phospho-cofilin, suggesting that misregulation of cofilin might affect adhesion dynamics. Slingshot-1L, a cofilin-activating phosphatase, localizes to focal adhesions and interacts with coronin 2A. Depletion of coronin 2A reduces cofilin activity at focal adhesions, as measured by barbed-end density and actin FRAP. In both fixed cells and live cells, cofilin localizes to the proximal end of some focal adhesions. Although expression of wild-type cofilin in coronin-2A-depleted cells has no major effect on focal-adhesion dynamics, expression of an active mutant of cofilin bypasses the defects in cell motility and focal-adhesion disassembly. These results implicate both coronin 2A and cofilin as factors that can regulate a subset of focal-adhesion-turnover events.
Marshall
Thomas W
TW
Lineberger Comprehensive Cancer Center and Department of Cell and Developmental Biology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
Aloor
Heather L
HL
Bear
James E
JE
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction
D051338:Cofilin 1; D008840:Microfilament Proteins; C072061:coronin proteins; C529152:SSH1 protein, rat; D010744:Phosphoric Monoester Hydrolases