Nitric oxide release from a single cell affects filopodial motility on growth cones of neighboring neurons.
Nitric oxide (NO), a gaseous messenger, has been reported to be involved in a variety of functions in the nervous system, ranging from neuronal pathfinding to learning and memory. We have shown previously that the application of NO via NO donors to growth cones of identified Helisoma buccal neurons B5 in vitro induces an increase in filopodial length, a decrease in filopodial number, and a slowing in neurite advance. It is unclear, however, whether NO released from a physiological source would affect growth cone dynamics. Here we used cell bodies of identified neurons known to express the NO synthesizing enzyme nitric oxide synthase (NOS) as a source of constitutive NO production and tested their effect on growth cones of other cells in a sender-receiver paradigm. We showed that B5 cell bodies induced a rapid increase in filopodial length in NO-responsive growth cones, and that this effect was blocked by the NOS inhibitor 7-NI, suggesting that the effect was mediated by NO. Inhibition of soluble guanylyl cyclase (sGC) with ODQ blocked filopodial elongation induced by B5 somata, confirming that NO acted via sGC. We also demonstrate that the effect of NO was reversible and that a cell releasing NO can affect growth cones over a distance of at least 100 microm. Our results suggest that NO released from a physiological source can affect the motility of nearby growth cones and thus should be considered a signaling molecule with the potential to affect the outcome of neuronal pathfinding in vivo.
Tornieri
Karine
K
Department of Biology, Georgia State University, Atlanta, GA 30302-4010, USA.
Rehder
Vincent
V
D000704:Analysis of Variance; D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D020439:Growth Cones / Q000187:drug effects / Q000648:ultrastructure*; D006372:Helix, Snails; D007191:Indazoles / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007191:Indazoles; D010069:Oxadiazoles; C522526:oxadiazol-3-one; D009569:Nitric Oxide; C080122:7-nitroindazole