title: Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase.
abstract: The c-Jun N-terminal kinase (JNK) is part of a stress signalling pathway strongly activated by NMDA-stimulation and involved in synaptic plasticity. Many studies have been focused on the post-synaptic mechanism of JNK action, and less is known about JNK presynaptic localization and its physiological role at this site. Here we examined whether JNK is present at the presynaptic site and its activity after presynaptic NMDA receptors stimulation. By using N-SIM Structured Super Resolution Microscopy as well as biochemical approaches, we demonstrated that presynaptic fractions contained significant amount of JNK protein and its activated form. By means of modelling design, we found that JNK, via the JBD domain, acts as a physiological effector on T-SNARE proteins; then using biochemical approaches we demonstrated the interaction between Syntaxin-1-JNK, Syntaxin-2-JNK, and Snap25-JNK. In addition, taking advance of the specific JNK inhibitor peptide, D-JNKI1, we defined JNK action on the SNARE complex formation. Finally, electrophysiological recordings confirmed the role of JNK in the presynaptic modulation of vesicle release. These data suggest that JNK-dependent phosphorylation of T-SNARE proteins may have an important functional role in synaptic plasticity.
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Biggi
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Buccarello
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sclip
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Lippiello
authors.affiliation: Sanipedia S.r.l., Via Ariosto 21, 20091 Bresso, Italy.
authors.forename: Noemi
authors.identifier: 0000-0002-4788-2413
authors.initials: N
authors.lastname: Tonna
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milano, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.affiliation: Department of Informatics, Institute of Computational Science, Università della Svizzera Italiana (USI), Via G. Bu 13, 6900 Lugano, Switzerland.
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Marino
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Maria Concetta
authors.identifier: 0000-0003-3844-0581
authors.initials: MC
authors.lastname: Miniaci
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milano, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milano, Italy.
authors.forename: Tiziana
authors.identifier: 0000-0002-0213-4040
authors.initials: T
authors.lastname: Borsello
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D005998:Glycine / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000201:enzymology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D050600:SNARE Proteins; D016202:N-Methylaspartate; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D005998:Glycine