JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked release

Yasunori Mori, Maiko Higuchi, Yusuke Hirabayashi, Mitsunori Fukuda, Yukiko Gotoh

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Ca2+ 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 Ca2+-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 Ca2+-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 Ca2+-evoked release by Syt 4. These results provide a molecular basis for the effect of growth factors on Ca2+-mediated secretion.

Original languageEnglish
Pages (from-to)76-87
Number of pages12
JournalEMBO Journal
Issue number1
Publication statusPublished - 2008 Jan 9


  • JNK
  • NGF
  • PC12 cells
  • Secretion
  • Synaptotagmin-4


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