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| Subject Categories: Membranes & Transport | Signal Transduction |
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| The EMBO Journal
(2008) 27, 76–87, doi:10.1038/sj.emboj.7601935 Published online 29 November 2007 |
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| JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked release |
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| Yasunori Mori1, Maiko Higuchi1, Yusuke Hirabayashi1, Mitsunori Fukuda2 and Yukiko Gotoh1 |
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1 Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan To whom correspondence should be addressed Yukiko Gotoh, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Tel.: +81 3 5841 8473; Fax: +81 3 5841 8472; E-mail: ygotoh@iam.u-tokyo.ac.jp Maiko Higuchi, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Tel.: +81 3 5841 8473; Fax: +81 3 5841 8472; E-mail: mhiguchi@iam.u-tokyo.ac.jp Received 27 April 2007; Accepted 6 November 2007; Published online 29 November 2007. |
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| Abstract |
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| 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 Ca2+-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. |
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| Keywords: JNK, NGF, PC12 cells, secretion, synaptotagmin-4 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article JNK phosphorylates synaptotagmin-4 and enhances Ca 2+ -evoked release The EMBO Journal Article Nature Biotechnology Research (01 Jan 2002) Differential regulation of c-Jun by ERK and JNK during PC12 cell differentiation The EMBO Journal Article (03 Aug 1998) POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis The EMBO Journal Article (15 Jan 2003) |
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