Hippocampal γCaMKII dopaminylation promotes synaptic-to-nuclear signaling and memory formation.

Autor:	Stewart AF; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Fulton SL; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Durand-de Cuttoli R; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Thompson RE; Department of Chemistry, Princeton, New Jersey 08544, USA., Chen PJ; Department of Pharmacological Sciences and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Brindley E; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Cetin B; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Farrelly LA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Futamura R; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Claypool S; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Bastle RM; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Di Salvo G; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands., Peralta C; The Rockefeller University Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA., Molina H; The Rockefeller University Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA., Baljinnyam E; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Marro SG; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Russo SJ; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., DeVita RJ; Department of Pharmacological Sciences and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Muir TW; Department of Chemistry, Princeton, New Jersey 08544, USA., Maze I; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; Department of Pharmacological Sciences and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 24. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1101/2024.09.19.613951
Abstrakt:	Protein monoaminylation is a class of posttranslational modification (PTM) that contributes to transcription, physiology and behavior. While recent analyses have focused on histones as critical substrates of monoaminylation, the broader repertoire of monoaminylated proteins in brain remains unclear. Here, we report the development/implementation of a chemical probe for the bioorthogonal labeling, enrichment and proteomics-based detection of dopaminylated proteins in brain. We identified 1,557 dopaminylated proteins - many synaptic - including γCaMKII, which mediates Ca 2+ -dependent cellular signaling and hippocampal-dependent memory. We found that γCaMKII dopaminylation is largely synaptic and mediates synaptic-to-nuclear signaling, neuronal gene expression and intrinsic excitability, and contextual memory. These results indicate a critical role for synaptic dopaminylation in adaptive brain plasticity, and may suggest roles for these phenomena in pathologies associated with altered monoaminergic signaling. Competing Interests: COMPETING INTERESTS The Authors declare no competing interests.
Databáze:	MEDLINE
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