Nitric oxide modulates intracellular translocation of pigment organelles in Xenopus laevis melanophores

Pigment organelles in Xenopus laevis melanophores are used by the animal to change skin color, and they provide a good model for studying intracellula r organelle transport. Movement of organelles and vesicles along the cytosk eleton is essential for many processes, such as axonal transport, endocytos is, and intercompartmental trafficking. Nitric oxide (NO) is a signaling mo lecule that plays a role in, among other things, relaxation of blood vessel s, sperm motility, and polymerization of actin. Our study focused on the ef fect NO exerts on cytoskeleton-mediated transport, which has previously rec eived little attention. We found that an inhibitor of NO synthesis, N-nitro -L-arginine methyl ester (L-NAME), reduced the melatonin-induced aggregatio n of the pigment organelles, melanosomes. Preaggregated melanosomes dispers ed after treatment with L-NAME but not after exposure to the inactive stere oisomer (D-NAME) or the substrate for NO synthesis (L-arginine). Signal tra nsduction by NO can be mediated through the activation of soluble guanylate cyclase (sGC), which leads to increased production of cGMP and activation of cGMP-dependent kinases (PKG). We found that both the sGC inhibitor 1H-(1 ,2,4) oxadiazolo(4,3-a)quinoxalin-1-one (ODQ) and the cGMP analogue 8-bromo guanosine 3':5'-cyclic monophosphate (8-Br-cGMP) reduced melanosome aggrega tion, whereas the PKG inhibitor KT582 did not. Our results demonstrate that melanosome aggregation depends on synthesis of NO, and NO deprivation caus es dispersion. It seems, thus, as if NO and cGMP are essential and can regu late melanosome translocation. (C) 2000 Wiley-Liss, Inc.