title: Nitric Oxide-Induced Calcium Release: Activation of Type 1 Ryanodine Receptor, a Calcium Release Channel, through Non-Enzymatic Post-Translational Modification by Nitric Oxide.
abstract: Nitric oxide (NO) is a typical gaseous messenger involved in a wide range of biological processes. In our classical knowledge, effects of NO are largely achieved by activation of soluble guanylyl cyclase to form cyclic guanosine-3', 5'-monophosphate. However, emerging evidences have suggested another signaling mechanism mediated by NO: "S-nitrosylation" of target proteins. S-nitrosylation is a covalent addition of an NO group to a cysteine thiol/sulfhydryl (RSH), and categorized into non-enzymatic post-translational modification (PTM) of proteins, contrasted to enzymatic PTM of proteins, such as phosphorylation mediated by various protein kinases. Very recently, we found novel intracellular calcium (Ca(2+)) mobilizing mechanism, NO-induced Ca(2+) release (NICR) in cerebellar Purkinje cells. NICR is mediated by type 1 ryanodine receptor (RyR1), a Ca(2+) release channel expressed in endoplasmic-reticular membrane. Furthermore, NICR is indicated to be dependent on S-nitrosylation of RyR1, and involved in synaptic plasticity in the cerebellum. In this review, molecular mechanisms and functional significance of NICR, as well as non-enzymatic PTM of proteins by gaseous signals, are described.
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto , Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
keywords: Purkinje cell; S-nitrosylation; calcium release; gaseous messenger; nitric oxide; post-translational modification; ryanodine receptor; synaptic plasticity