Laminin-1 activates Cdc42 in the mechanism of laminin-1-mediated neurite outgrowth

Here, we investigated the role of the small Rho GTPases Rac, Cdc42, and Rho in the mechanism of laminin-l-mediated neurite outgrowth in PC12 cells. PC 12 cells were transfected with plasmids expressing wildtype and dominant-ne gative mutants of Rac (RacN17), Cdc42 (Cdc42N17), or Rho (RhoN19). Over 90% of the dominant-negative Rho- and Rac-transfected cells extended neurites when plated on laminin-l; however, none of the PC12 cells transfected with the dominant-negative Cdc42 mutant extended neurites. In cells cotransfecte d with plasmids expressing c-Jun N-terminal kinase and wild-type Cdc42, lam inin-l treatment stimulated detectable levels of c-Jun phosphorylation. Fur ther, cotransfection with c-Jun N-terminal kinase and the dominant-negative Cdc42 mutant blocked laminin-l-mediated c-Jun phosphorylation. Transfectio n with either wild-type Rac or the dominant-negative Rac did not effect c-J un phosphorylation. These data demonstrate that Cdc42 is activated by lamin in-l and that Cdc42 activation is required in the mechanism of laminin-l-me diated neurite outgrowth. (C) 2000 Academic Press.