ACTIVATED MUTANTS OF THE ALPHA-SUBUNIT OF G(0) PROMOTE AN INCREASED NUMBER OF NEURITES PER CELL

The high concentration of the GTP-binding protein G(o) in the neuronal growth cone suggests that G(o) activation state may alter neurite out growth. We find that activation of pertussis toxin-sensitive G-protein s by mastoparan increases neurite outgrowth from neuroblastoma cells. To examine G(o) activation specifically, point mutations homologous to activating, oncogenic mutations in alpha a(i2) and alpha(s) were intr oduced into the alpha subunit of G(o). The stability of the alpha(o), mutants to tryptic digestion confirms that they are activated. When ex pressed in PC12 or N1E-115 cells, activated alpha(o), doubles total ne urite length per cell, primarily by increasing the number of neurites per cell. The growth cones of cells expressing activated alpha(o) are narrower than control growth cones. Expression of wild-type alpha(o) o r the activated alpha subunits of other G-proteins did not affect tota l neurite length per cell. Thus, factors that lead to activation of G( o) can modulate neurite number per cell.