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Journal of Neuroscience, Vol 14, 2327-2338, Copyright © 1994 by Society for Neuroscience
Activated mutants of the alpha subunit of G(o) promote an increased number of neurites per cell
SM Strittmatter, MC Fishman and XP Zhu
Developmental Biology Laboratory, Massachusetts General Hospital, Charleston.
The high concentration of the GTP-binding protein G(o) in the neuronal
growth cone suggests that G(o) activation state may after neurite
outgrowth. We find that activation of pertussis toxin-sensitive G- proteins
by mastoparan increases neurite outgrowth from neuroblastoma cells. To
examine G(o) activation specifically, point mutations homologous to
activating, oncogenic mutations in alpha i2 and alpha s were introduced
into the alpha subunit of G(o). The stability of the alpha o mutants to
tryptic digestion confirms that they are activated. When expressed in PC12
or N1E-115 cells, activated alpha o doubles total neurites 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 wildtype alpha o or the activated alpha subunits of
other G-proteins did not affect total neurite length per cell. Thus,
factors that lead to activation of G(o) can modulate neurite number per
cell.
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