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JNK phosphorylates synaptotagmin‐4 and enhances Ca 2+ ‐evoked release
Author(s) -
Mori Yasunori,
Higuchi Maiko,
Hirabayashi Yusuke,
Fukuda Mitsunori,
Gotoh Yukiko
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601935
Subject(s) - synaptotagmin 1 , biology , exocytosis , microbiology and biotechnology , synaptotagmin i , secretory vesicle , synaptic vesicle , phosphorylation , depolarization , nerve growth factor , long term potentiation , secretion , vesicle , endocrinology , biochemistry , receptor , membrane
Ca 2+ influx induced by membrane depolarization triggers the exocytosis of secretory vesicles in various cell types such as endocrine cells and neurons. Peptidyl growth factors enhance Ca 2+ ‐evoked release, an effect that may underlie important adaptive responses such as the long‐term potentiation of synaptic transmission induced by growth factors. Here, we show that activation of the c‐Jun N‐terminal kinase (JNK) plays an essential role in nerve growth factor (NGF) enhancement of Ca 2+ ‐evoked release in PC12 neuroendocrine cells. Moreover, JNK associated with phosphorylated synaptotagmin‐4 (Syt 4), a key mediator of NGF enhancement of Ca 2+ ‐evoked release in this system. NGF treatment led to phosphorylation of endogenous Syt 4 at Ser135 and translocation of Syt 4 from immature to mature secretory vesicles in a JNK‐dependent manner. Furthermore, mutation of Ser135 abrogated enhancement of Ca 2+ ‐evoked release by Syt 4. These results provide a molecular basis for the effect of growth factors on Ca 2+ ‐mediated secretion.