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Neural Plasticity
Volume 2017, Article ID 6468356, 14 pages
https://doi.org/10.1155/2017/6468356
Research Article

Evidence of Presynaptic Localization and Function of the c-Jun N-Terminal Kinase

1IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milano, Italy
2Department of Pharmacy, University of Naples Federico II, Naples, Italy
3Sanipedia S.r.l., Via Ariosto 21, 20091 Bresso, Italy
4Department of Pharmacological and Biomolecular Sciences, University of Milan, Milano, Italy
5Department of Informatics, Institute of Computational Science, Università della Svizzera Italiana (USI), Via G. Bu 13, 6900 Lugano, Switzerland

Correspondence should be addressed to Tiziana Borsello; ti.irgenoiram@ollesrob.anaizit

Received 5 August 2016; Revised 28 October 2016; Accepted 15 December 2016; Published 7 March 2017

Academic Editor: Christian Wozny

Copyright © 2017 Silvia Biggi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.