Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide.
Nitric oxide, a free-radical gas produced endogenously by several mammalian cell types, has been implicated as a diffusible intercellular messenger subserving use-dependent modification of synaptic efficacy in the mature central nervous system. It has been suggested on theoretical grounds that nitric oxide might play an analogous role during the establishment of ordered connections by developing neurons. We report here that nitric oxide rapidly and reversibly inhibits growth of neurites of rat dorsal root ganglion neurons in vitro. In addition, we show that exposure to nitric oxide inhibits thioester-linked long-chain fatty acylation of neuronal proteins, possibly through a direct modification of substrate cysteine thiols. Our results demonstrate a potential role for nitric oxide in the regulation of process outgrowth and remodelling during neuronal development, which may be effected at least in part through modulation of dynamic protein fatty acylation in neuronal growth cones.
Hess
D T
DT
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Patterson
S I
SI
Smith
D S
DS
Skene
J H
JH
D000215:Acylation; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000494:pharmacology*; D016716:PC12 Cells; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D006454:Hemoglobins; D009419:Nerve Tissue Proteins; D010169:Palmitic Acids; D014665:Vasodilator Agents; D019308:Palmitic Acid; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP