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Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 cells.

Mitsunori Fukuda·Judith A Kowalchyk·Xiaodong Zhang·Thomas F J Martin·Katsuhiko Mikoshiba
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Abstract

Synaptotagmin (Syt) I-deficient phaeochromocytoma (PC12) cell lines show normal Ca(2+)-dependent norepinephrine (NE) release (Shoji-Kasai, Y., Yoshida, A., Sato, K., Hoshino, T., Ogura, A., Kondo, S., Fujimoto, Y., Kuwahara, R., Kato, R., and Takahashi, M. (1992) Science 256, 1821-1823). To identify an alternative Ca(2+) sensor, we searched for other Syt isoforms in Syt I-deficient PC12 cells and identified Syt IX, an isoform closely related to Syt I, as an abundantly expressed dense-core vesicle protein. Here we show that Syt IX is required for the Ca(2+)-dependent release of NE from PC12 cells. Antibodies directed against the C2A domain of either Syt IX or Syt I inhibited Ca(2+)-dependent NE release in permeable PC12 cells indicating that both Syt proteins function in dense-core vesicle exocytosis. Our results support the idea that Syt family proteins that co-reside on secretory vesicles may function cooperatively and redundantly as potential Ca(2+) sensors for exocytosis.

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AnimalsCOS CellsCalciumCalcium-Binding ProteinsDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelExocytosisMembrane GlycoproteinsNerve Tissue ProteinsPC12 CellsPhylogenyProtein BindingProtein IsoformsProtein Structure, TertiaryRatsRecombinant ProteinsSynaptotagminsTime FactorsTissue DistributionJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Mitsunori Fukuda, Judith A Kowalchyk, Xiaodong Zhang, Thomas F J Martin, Katsuhiko Mikoshiba. 2001-12-21. Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 cells.. https://doi.org/10.1074/jbc.c100588200

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