Synaptotagmin IX Regulates Ca2+-dependent Secretion in PC12 Cells*

Synaptotagmin (Syt) I-deficient phaeochromocytoma (PC12) cell lines show normal Ca2+-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 Ca2+ 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 Ca2+-dependent release of NE from PC12 cells. Antibodies directed against the C2A domain of either Syt IX or Syt I inhibited Ca2+-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 Ca2+ sensors for exocytosis.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-02-15

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.C100588200PMID 11751925
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release.

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  1999cited by this paper
• A Novel Alternatively Spliced Variant of Synaptotagmin VI Lacking a Transmembrane Domain

  1999cited by this paper
• Synaptotagmins: more isoforms than functions?

  1998cited by this paper
• Presynaptic injection of syntaxin-specific antibodies blocks transmission in the squid giant synapse.

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• The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic β‐cells: action of synaptotagmin at low micromolar calcium

  1997cited by this paper
• Regulation by bivalent cations of phospholipid binding to the C2A domain of synaptotagmin III.

  1997cited by this paper
• The function of inositol high polyphosphate binding proteins

  1997cited by this paper
• Roles of synaptotagmin C2 domains in neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses.

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• Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of exocytosis in adrenal chromaffin cells.

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• Doc2 Enhances Ca-dependent Exocytosis from PC12 Cells (*)

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• Phospholipid Composition Dependence of Ca-dependent Phospholipid Binding to the C2A Domain of Synaptotagmin IV (*)

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• Synaptotagmin V: a novel synaptotagmin isoform expressed in rat brain

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• Essential functions of synapsins I and II in synaptic vesicle regulation

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• Synaptic vesicle dynamics in living cultured hippocampal neurons visualized with CY3-conjugated antibodies directed against the lumenal domain of synaptotagmin

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• Identification of a nonneuronal isoform of synaptotagmin.

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• Role of the C2A domain of synaptotagmin in transmitter release as determined by specific antibody injection into the squid giant synapse preterminal.

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• Evidence That the Rab3a-binding Protein, Rabphilin3a, Enhances Regulated Secretion.

  1995cited by this paper
• The molecular machinery for fast and slow neurosecretion.

  1994cited by this paper
• A role for synaptotagmin (p65) in regulated exocytosis.

  1993cited by this paper
• Resolution of regulated secretion into sequential MgATP-dependent and calcium-dependent stages mediated by distinct cytosolic proteins

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• Cell cracking: permeabilizing cells to macromolecular probes.

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• Synaptotagmin IV function in secretory granule maturation in neuroendocrine cells.

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