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http://purl.uniprot.org/citations/29630591http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29630591http://www.w3.org/2000/01/rdf-schema#comment"Nitric oxide (NO) regulates neuronal function and thus is critical for tuning neuronal communication. Mechanisms by which NO modulates protein function and interaction include posttranslational modifications (PTMs) such as S-nitrosylation. Importantly, cross signaling between S-nitrosylation and prenylation can have major regulatory potential. However, the exact protein targets and resulting changes in function remain elusive. Here, we interrogated the role of NO-dependent PTMs and farnesylation in synaptic transmission. We found that NO compromises synaptic function at the Drosophila neuromuscular junction (NMJ) in a cGMP-independent manner. NO suppressed release and reduced the size of available vesicle pools, which was reversed by glutathione (GSH) and occluded by genetic up-regulation of GSH-generating and de-nitrosylating glutamate-cysteine-ligase and S-nitroso-glutathione reductase activities. Enhanced nitrergic activity led to S-nitrosylation of the fusion-clamp protein complexin (cpx) and altered its membrane association and interactions with active zone (AZ) and soluble N-ethyl-maleimide-sensitive fusion protein Attachment Protein Receptor (SNARE) proteins. Furthermore, genetic and pharmacological suppression of farnesylation and a nitrosylation mimetic mutant of cpx induced identical physiological and localization phenotypes as caused by NO. Together, our data provide evidence for a novel physiological nitrergic molecular switch involving S-nitrosylation, which reversibly suppresses farnesylation and thereby enhances the net-clamping function of cpx. These data illustrate a new mechanistic signaling pathway by which regulation of farnesylation can fine-tune synaptic release."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.org/dc/terms/identifier"doi:10.1371/journal.pbio.2003611"xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Smith T.M."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Mistry R."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Breda C."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Robinson S.W."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Morone N."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Giorgini F."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Dinsdale D."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Mallucci G.R."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Campesan S."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Butcher A."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Steinert J.R."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Bourgognon J.M."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Challiss R.A.J."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Guerra-Martin M."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/author"Spiers J.G."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/name"PLoS Biol"xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/pages"e2003611"xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/title"Nitric oxide-mediated posttranslational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability."xsd:string
http://purl.uniprot.org/citations/29630591http://purl.uniprot.org/core/volume"16"xsd:string
http://purl.uniprot.org/citations/29630591http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29630591
http://purl.uniprot.org/citations/29630591http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29630591