Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells.

Schuichi Koizumi, Patrizia Rosa, Gary B. Willars, R. A.John Challiss, Elena Taverna, Maura Francolini, Martin D. Bootman, Peter Lipp, Kazuhide Inoue, John Roder, Andreas Jeromin

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Abstract

Neuronal calcium sensor-1 (NCS-1) or the originally identified homologue frequenin belongs to a superfamily of EF-hand calcium binding proteins. Although NCS-1 is thought to enhance synaptic efficacy or exocytosis mainly by activating ion channel function, the detailed molecular basis for the enhancement is still a matter of debate. Here, mechanisms underlying the NCS-1-evoked enhancement of exocytosis were investigated using PC12 cells overexpressing NCS-1. NCS-1 was found to have a broad distribution in the cells being partially distributed in the cytosol and associated to vesicles and tubular-like structures. Biochemical and immunohistochemical studies indicated that NCS-1 partially colocalized with the light synaptic vesicle marker synaptophysin. When stimulated with UTP or bradykinin, agonists to phospholipase C-linked receptors, NCS-1 enhanced the agonist-mediated elementary and global Ca2+ signaling and increased the levels of downstream signals of phosphatidylinositol 4-kinase. NCS-1 enhanced the UTP-evoked exocytosis but not the depolarization-evoked Ca2+ responses or exocytosis, suggesting that the enhancement by NCS-1 should involve phospholipase C-linked receptor-mediated signals rather than the Ca2+ channels or exocytotic machinery per se. Taken together, NCS-1 enhances phosphoinositide turnover, resulting in enhancement of Ca2+ signaling and exocytosis. This is a novel regulatory mechanism of exocytosis that might involve the activation of phosphatidylinositol 4-kinase.

Original languageEnglish
Pages (from-to)30315-30324
Number of pages10
JournalThe Journal of biological chemistry
Volume277
Issue number33
DOIs
Publication statusPublished - Aug 16 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Koizumi, S., Rosa, P., Willars, G. B., Challiss, R. A. J., Taverna, E., Francolini, M., Bootman, M. D., Lipp, P., Inoue, K., Roder, J., & Jeromin, A. (2002). Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells. The Journal of biological chemistry, 277(33), 30315-30324. https://doi.org/10.1074/jbc.M201132200