Regulation of neuronal growth cone filopodia by nitric oxide depends on soluble guanylyl cyclase.
Nitric oxide has been proposed to play an important role in neuronal development. We have previously shown that growth cones from an identified neuron, B5, in the snail Helisoma trivolvis, respond to nitric oxide (NO) donors by increasing the length of their filopodia within minutes of application (Van Wagenen and Rehder, 1999). This effect was mediated through a cGMP-induced increase in [Ca2+]i and resulted in an enlargement of the growth cone's action radius, suggesting that NO could function as a signaling molecule during neuronal pathfinding. We show here that NO functions as a specific rather than a general regulator of growth cone filopodia, because another identified neuron from the same ganglion, B19, failed to respond to NO with an increase in filopodial length. We found that, contrary to B5 neurons, B19 growth cones contained little or no soluble guanylyl cyclase (sGC) immunoreactivity, presumably preventing their response to NO. This hypothesis was supported by the finding that the sGC activator YC-1 (10 microM) had no effect on B19 filopodia but induced elongation of B5 filopodia. These results indicate that the effects of NO can be quite specific, and raise the interesting possibility that neurons could selectively tune in to NO by differentially expressing the target enzyme sGC in the appropriate cellular location during critical developmental stages. In addition, our NADPH-diaphorase staining and anti-NOS immunohistochemisty suggest that growth cones of B5 neurons, but not of B19 neurons, could be a source of NO, making NO a potential intra- and transcellular messenger.
Van Wagenen
S
S
Biology Department, Georgia State University, Atlanta, Georgia 30303, USA.
Rehder
V
V
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006162:Guanylate Cyclase / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012908:Snails / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism
D020030:Nitric Oxide Donors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D011189:Potassium Chloride; D008981:Molsidomine; D009252:NADPH Dehydrogenase; D006162:Guanylate Cyclase; D006152:Cyclic GMP