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

Scientific Reports
Robert NisticòMarco Feligioni

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.

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Citations

Jan 5, 2016·Trends in Neurosciences·Abhishek BanerjeeOle Paulsen
Sep 19, 2016·Acta Neuropathologica Communications·Sabine SellnerThomas Blank
Oct 16, 2016·Molecular Neurobiology·Serena MarcelliMarco Feligioni
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Nov 4, 2020·The Journal of Physiology·Hovy Ho-Wai WongP Jesper Sjöström
Aug 9, 2021·Neuropharmacology·Qi-Yu ChenMin Zhuo

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Methods Mentioned

BETA
electron microscopy
Confocal microscopy
transgenic

Software Mentioned

Imaris Surface
GraphPad
Niss Elements
ImarisColoc
Imaris Suite
pClamp10
GraphPad PRISM
ImarisSuite
ImageJ
Plot Profile

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