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© The Rockefeller University Press, 0021-9525/2000//1159 $5.00
The Journal of Cell Biology, Volume 148, Number 6, , 2000 1159-1164

Hyaluronic Acid (Ha) Binding to Cd44 Activates Rac1 and Induces Lamellipodia Outgrowth

^a Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria
^b Institute of Molecular Biology, Austrian Academy of Sciences, A-5020 Salzburg, Austria
IMP, Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.(+43)-1-7987-153(+43)-1-79730-885

huber{at}nt.imp.univie.ac.at

Both cell adhesion protein CD44 and its main ligand hyaluronic acid (HA) are thought to be involved in several processes ultimately requiring cytoskeleton rearrangements. Here, we show that the small guanine nucleotide (GTP)-binding protein, Rac1, can be activated upon HA binding to CD44. When applied locally to a passive cell edge, HA promoted the formation of lamellipodial protrusions in the direction of the stimulus. This process was inhibited by the prior injection of cells with dominant-negative N17Rac recombinant protein or by pretreatment of cells with monoclonal anti-CD44 antibodies, interfering with HA binding, implying the direct involvement of CD44 in signaling to Rac1.

Key Words: extracellular matrix • cell guidance • Rac1 • cytoskeleton • mammary epithelial cells

© 2000 The Rockefeller University Press

Abbreviations used in this paper: EpH4, mouse mammary epithelial cell line; HA, hyaluronic acid.

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