Journal
CELL COMMUNICATION AND ADHESION
Volume 9, Issue 5-6, Pages 273-283Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15419060216306
Keywords
focal adhesions; hyaluronan; lamellae; motility; RHAMM; Src
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Exogenous hyaluronan promotes a rapid recruitment of Src to lamellae of mutant active H-ras transformed fibroblasts and an Src- and RHAMM (CD168)-dependent increase in random motility. These responses are accompanied by a loss of vinculin-positive lamellae focal adhesions. Nontransformed immortalized wild-type fibroblasts (WT) do not increase random motility in response to hyaluronan alone, but do increase motility in response to a combination of PMA treatment followed by hyaluronan. PMA treatment alone increases the number of lamellae/cell, percentage of cells with lamellae and number of focal adhesions/lamellae. Subsequent addition of hyaluronan does not affect the number of lamellae/cell but reduces both the number of focal adhesion/lamellae and the percentage of cells forming focal adhesion-positive lamellae. These effects are prevented by blocking RHAMM antibodies and mimicked by agonist RHAMM antibodies. Src-/- fibroblasts exhibit a limited response to PMA but do not increase motility or disassemble focal adhesions in response to a subsequent addition of HA. Rescue of Src-/- fibroblasts with either SrcA or c-Src restores response to close to WT levels. These results suggest that Src activity is uniquely required for both PMA and PMA-induced hyaluronan regulation of random motility and focal adhesion turnover.
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