Cerebellar localization of the NO-receptive soluble guanylyl cyclase subunits-α2/β1 in non-human primates

Nitric-oxide-sensitive guanylyl cyclase (NO-sGC) plays a pivotal role in many second messenger cascades. Neurotransmission- and neuropathology-related changes in NO-sGC have been suggested. However, the cellular localization of NO-sGC in primate brains, including humans, remains unknown. Biochemical evidence has linked the alpha(2)-subunit of NO-sGC directly to neurotransmission in rodents. Here, we have used a recently characterized subunit-specific antibody for the localization of the a2-subunit on sections from the cerebelli of the common marmoset (Callithrix jacchus; New World monkey) and macaque monkeys (Macaca mulatta, M fascicularis; Old World monkeys). In contrast to the more ubiquitous cytoplasmic presence of subunit-P 1, the a2-subunit is mainly confined to the somato-dendritic membrane including the spines of the Purkinje cells. Only limited colocalization with presynaptically localized synaptophysin has been seen under our staining conditions, indicating a higher abundance of subunit-alpha(2) at the postsynaptic site. This localization indicates that subunit-alpha(2) links NO-sGC to neurotransmission, whereas subunit-beta(1) may act as a cytoplasmic regulator/activator by contributing to active heterodimer formation via translocation from the cytoplasm to the cell membrane. The last-mentioned action may be a prerequisite for generating nitric-oxide-dependent, subcellular, and postsynaptically localized cGMP signals along neuronal processes.