title: Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release.
abstract: Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a critical step for neuronal death occurring in several neurological conditions. JNKs can be activated via receptor tyrosine kinases, cytokine receptors, G-protein coupled receptors and ligand-gated ion channels, including the NMDA glutamate receptors. While JNK has been generally associated with postsynaptic NMDA receptors, its presynaptic role remains largely unexplored. Here, by means of biochemical, morphological and functional approaches, we demonstrate that JNK and its scaffold protein JIP1 are also expressed at the presynaptic level and that the NMDA-evoked glutamate release is controlled by presynaptic JNK-JIP1 interaction. Moreover, using knockout mice for single JNK isoforms, we proved that JNK2 is the essential isoform in mediating this presynaptic event. Overall the present findings unveil a novel JNK2 localization and function, which is likely to play a role in different physiological and pathological conditions.
authors.affiliation: 1] Laboratory of Pharmacology of Synaptic Plasticity, EBRI "Rita Levi-Montalcini" Foundation, Rome, 00143, Italy [2] Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 00185, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.affiliation: Laboratory of Pharmacology of Synaptic Plasticity, EBRI "Rita Levi-Montalcini" Foundation, Rome, 00143, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.affiliation: 1] Laboratory of Pharmacology of Synaptic Plasticity, EBRI "Rita Levi-Montalcini" Foundation, Rome, 00143, Italy [2] Laboratory of Experimental Neurology, IRCCS Fondazione Santa Lucia, Rome, 00143, Italy.
authors.forename: Dalila
authors.initials: D
authors.lastname: Mango
authors.affiliation: Laboratory of Pharmacology of Synaptic Plasticity, EBRI "Rita Levi-Montalcini" Foundation, Rome, 00143, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ferraina
authors.affiliation: Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, 16148, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.affiliation: Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, 16148, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Prisco
authors.affiliation: 1] Laboratory of Experimental Neurology, IRCCS Fondazione Santa Lucia, Rome, 00143, Italy [2] University Campus Biomedico, 00100 Rome.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nobili
authors.affiliation: Neuropathology &Neurology V - IRCCS Foundation C. Besta Milan, 20133, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Saccucci
authors.affiliation: 1] Laboratory of Experimental Neurology, IRCCS Fondazione Santa Lucia, Rome, 00143, Italy [2] University Campus Biomedico, 00100 Rome.
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.affiliation: Neuropathology &Neurology V - IRCCS Foundation C. Besta Milan, 20133, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.affiliation: 1] Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, 16148, Italy [2] Center of Excellence for Biomedical Research, University of Genoa, Genoa, 16132, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
authors.affiliation: Laboratory of Experimental Neurology, IRCCS Fondazione Santa Lucia, Rome, 00143, Italy.
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, 01605, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.affiliation: 1] Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, 16148, Italy [2] Center of Excellence for Biomedical Research, University of Genoa, Genoa, 16132, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.affiliation: Laboratory of Pharmacology of Synaptic Plasticity, EBRI "Rita Levi-Montalcini" Foundation, Rome, 00143, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Feligioni
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004789:Enzyme Activation; D005089:Exocytosis; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D059008:Time-Lapse Imaging
chemical_list: D015415:Biomarkers; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D048056:Mitogen-Activated Protein Kinase 9