title: Cerebellar localization of the NO-receptive soluble guanylyl cyclase subunits-alpha(2)/beta (1) in non-human primates.
abstract: 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 alpha(2)-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-beta(1), the alpha(2)-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.
authors.affiliation: C.& O. Vogt Institute of Brain Research, Bldg. 22.03, University St. 1, 40225 Düsseldorf, Germany. hjb@hirn.uni-duesseldorf.de
authors.forename: Hans-J
authors.initials: HJ
authors.lastname: Bidmon
authors.forename: Hartmut
authors.initials: H
authors.lastname: Mohlberg
authors.forename: Gunnar
authors.initials: G
authors.lastname: Habermann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Buse
authors.forename: Karl
authors.initials: K
authors.lastname: Zilles
authors.forename: Sönke
authors.initials: S
authors.lastname: Behrends
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D064026:Calbindins; D002144:Callithrix; D002531:Cerebellum / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011323:Primates / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000201:enzymology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D064026:Calbindins; C000605660:GUCY1A2 protein, human; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D064030:S100 Calcium Binding Protein G; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP