title: G-substrate: the cerebellum and beyond.
abstract: The discovery of nitric oxide (NO) as an activator of soluble guanylate cyclase (sGC) has stimulated extensive research on the NO-sGC-3':5'-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) pathway. However, the restricted localization of pathway components and the lack of information on PKG substrates have hindered research seeking to examine the physiological roles of the NO-sGC-cGMP-PKG pathway. An excellent substrate for PKG is the G-substrate, which was originally discovered in the cerebellum. The role of G-substrate in the cerebellum and other brain structures has been revealed in recent years. This review discusses the relationship between the G-substrate and other components of the NO-sGC-cGMP-PKG pathway and describes the characteristics of the G-substrate gene and protein related to diseases. Finally, we discuss the physiological role of G-substrate in the cerebellum, where it regulates cerebellum-dependent long-term memory, and its role in the ventral tegmental area and retina, where it acts as an effective neuroprotectant.
authors.affiliation: Aging Regulation Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Endo
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000502:physiology; D025042:Amacrine Cells / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002493:Central Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D036881:Long-Term Synaptic Depression / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000071756:Soluble Guanylyl Cyclase; D017557:Ventral Tegmental Area / Q000502:physiology; D014828:Vocalization, Animal / Q000502:physiology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP