Hyaluronic acid (HA) binding to CD44 activates Rac1 and induces lamellipodia outgrowth

Both cell adhesion protein CD44 and its main ligand hyaluronic acid (HA) ar e thought to be involved in several processes ultimately requiring cytoskel eton rearrangements. Here, we show that the small guanine nucleotide (GTP)- binding protein, Rac1,can be activated upon HA binding to CD44. When applie d locally to a passive cell edge, HA promoted the formation of lamellipodia l protrusions in the direction of the stimulus. This process was inhibited by the prior injection of cells with dominant-negative N17Rac recombinant p rotein or by pretreatment of cells with monoclonal anti-CD44 antibodies, in terfering with HA binding, implying the direct involvement of CD44 in signa ling to Rac1.