JNK3 Couples the Neuronal Stress Response to Inhibition of Secretory Trafficking
| Autor: | Guang Yang, Si Zhang, Xun Zhou, Luba Kojic, William Jia, Ainsley Coquinco, Jingyan Zhu, Max S. Cynader, Yanhua Wen, Rui Liu, Yongting Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
N-Methylaspartate
Lipoylation the Golgi complex Biological Transport Active Golgi Apparatus AMPA receptor Editorials: Cell Cycle Features Biology Biochemistry GluR1 symbols.namesake Palmitoylation Mitogen-Activated Protein Kinase 10 Stress Physiological Chlorocebus aethiops Excitatory Amino Acid Agonists Animals palmitoylation Secretion Receptors AMPA zDHHC17 Rats Wistar Kinase activity Sac1 Molecular Biology Neurons palmitoyl acyltransferase Inositol Polyphosphate 5-Phosphatases Glutamate receptor PI4P stress response Cell Biology Golgi apparatus synaptoprotection Phosphoric Monoester Hydrolases Rats Cell biology Secretory protein nervous system COS Cells Mutation Synapses symbols NMDA receptor JNK Peptides Acyltransferases |
| Zdroj: | Cell Cycle |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.2003727 |
| Popis: | Secretory trafficking through the Golgi complex is critical for neuronal development, function, and stress response. Altered secretion is associated with the pathogenesis of various neurological diseases. We found that c-Jun amino-terminal kinase 3 (JNK3) inhibited secretory trafficking by promoting the depletion of phosphatidylinositol 4-phosphate (PI4P) in the Golgi complex of COS7 cells and primary rat neurons. Exposure of cultured primary rat neurons to excitotoxic concentrations of NMDA (N-methyl-d-aspartate), an agonist of a class of ionotropic glutamate receptors, or overexpression of zD17 (a palmitoyl transferase) resulted in JNK3 palmitoylation and association with the Golgi complex. Analysis of mutant constructs of JNK3 indicated that Golgi association was independent of its kinase activity but depended on its palmitoylation. The association of JNK3 with the Golgi in cultured neurons decreased the secretory trafficking of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 (glutamate receptor subunit 1), a component of ionotropic glutamate receptors found at glutamatergic synapses. Palmitoylated JNK3 bound to the phosphatase Sac1, increasing its abundance at the Golgi and thereby decreasing the abundance of PI4P, a lipid necessary for post-Golgi trafficking. Disrupting the JNK3-Sac1 interaction with two synthetic peptides prevented the loss of surface GluR1 and preserved synaptic integrity in cultured neurons exposed to NMDA. Together, our results suggest that JNK3 participates in an adaptive response to neuronal hyperexcitation by impeding secretory trafficking at the Golgi complex. |
| Databáze: | OpenAIRE |
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