Research ArticleNeuroscience

JNK3 Couples the Neuronal Stress Response to Inhibition of Secretory Trafficking

Science Signaling  09 Jul 2013:
Vol. 6, Issue 283, pp. ra57
DOI: 10.1126/scisignal.2003727

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JNK3 Golgi Traffic Cop in Neurons

Neuronal integrity is maintained by the secretory pathway. The phosphatase Sac1, which metabolizes phosphatidylinositol 4-phosphate (PI4P), inhibits the trafficking of proteins through the secretory pathway by depleting PI4P at the Golgi. Yang et al. found that JNK3 (c-Jun N-terminal kinase 3) was palmitoylated and associated with the Golgi in neurons exposed to NMDA (N-methyl-d-aspartate), a glutamate receptor agonist that can be excitotoxic. Independently of its kinase activity, JNK3 bound to Sac1 and sequestered it at the Golgi, resulting in decreased abundance of PI4P and inhibition of Golgi-to-surface trafficking of AMPA-type GluR1 (glutamate receptor subunit 1). Inhibiting the JNK3-Sac1 interaction with synthetic peptides prevented NMDA-induced reduction of surface GluR1 and synaptic loss. Thus, JNK3 appears to function in the neuronal response to stress to limit trafficking through the secretory pathway.