NEURONAL GROWTH CONE COLLAPSE AND INHIBITION OF PROTEIN FATTY ACYLATION BY NITRIC-OXIDE

NITRIC oxide, a free-radical gas produced endogenously by several mamm alian cell types1-6, has been implicated as a diffusible intercellular messenger subserving use-dependent modification of synaptic efficacy in the mature central nervous system7-10. It has been suggested on the oretical grounds that nitric oxide might play an analogous role during the establishment of ordered connections by developing neurons11. We report here that nitric oxide rapidly and reversibly inhibits growth o f neurites of rat dorsal root ganglion neurons in vitro. In addition, we show that exposure to nitric oxide inhibits thioester-linked long-c hain fatty acylation of neuronal proteins, possibly through a direct m odification of substrate cysteine thiols. Our results demonstrate a po tential role for nitric oxide in the regulation of process outgrowth a nd remodelling during neuronal development, which may be effected at l east in part through modulation of dynamic protein fatty acylation in neuronal growth cones.