Program in Molecular Medicine
Animals; Biomarkers; Cerebral Cortex; Enzyme Activation; Exocytosis; Female; Glutamic Acid; Male; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 9; Phosphorylation; Presynaptic Terminals; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptosomes; Time-Lapse Imaging
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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.
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DOI of Published Version
Sci Rep. 2015 Mar 12;5:9035. doi: 10.1038/srep09035. Link to article on publisher's site
Nistico, Robert; Florenzano, Fulvio; Mango, Dalila; Ferraina, Caterina; Grilli, Massimo; Di Prisco, Silvia; Nobili, Annalisa; Saccucci, Stefania; D'Amelio, Marcello; Morbin, Michela; Marchi, Mario; Mercuri, Nicola B.; Davis, Roger J.; Pittaluga, Anna; and Feligioni, Marco, "Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release" (2015). Davis Lab Publications. 52.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.