Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release

Robert Nisticò, Fulvio Florenzano, Dalila Mango, Caterina Ferraina, Massimo Grilli, Silvia Di Prisco, Annalisa Nobili, Stefania Saccucci, Marcello D'Amelio, Michela Morbin, Mario Marchi, Nicola B. Mercuri, Roger J. Davis, Anna Pittaluga, Marco Feligioni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number9035
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

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Mitogen-Activated Protein Kinase 9
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Phosphotransferases
Protein Isoforms
Ligand-Gated Ion Channels
Cytokine Receptors
JNK Mitogen-Activated Protein Kinases
Glutamate Receptors
Receptor Protein-Tyrosine Kinases
N-Methylaspartate
G-Protein-Coupled Receptors
Knockout Mice
Proteins

ASJC Scopus subject areas

  • General

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Nisticò, R., Florenzano, F., Mango, D., Ferraina, C., Grilli, M., Di Prisco, S., ... Feligioni, M. (2015). Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release. Scientific Reports, 5, [9035]. https://doi.org/10.1038/srep09035

Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release. / Nisticò, 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; Feligioni, Marco.

In: Scientific Reports, Vol. 5, 9035, 2015.

Research output: Contribution to journalArticle

Nisticò, R, Florenzano, F, Mango, D, Ferraina, C, Grilli, M, Di Prisco, S, Nobili, A, Saccucci, S, D'Amelio, M, Morbin, M, Marchi, M, Mercuri, NB, Davis, RJ, Pittaluga, A & Feligioni, M 2015, 'Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release', Scientific Reports, vol. 5, 9035. https://doi.org/10.1038/srep09035
Nisticò R, Florenzano F, Mango D, Ferraina C, Grilli M, Di Prisco S et al. Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release. Scientific Reports. 2015;5. 9035. https://doi.org/10.1038/srep09035
Nisticò, 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 ; Feligioni, Marco. / Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release. In: Scientific Reports. 2015 ; Vol. 5.
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