TY - JOUR
T1 - Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 cells
AU - Fukuda, Mitsunori
AU - Kowalchyk, Judith A.
AU - Zhang, Xiaodong
AU - Martin, Thomas F.J.
AU - Mikoshiba, Katsuhiko
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/2/15
Y1 - 2002/2/15
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.C100588200
DO - 10.1074/jbc.C100588200
M3 - Article
C2 - 11751925
AN - SCOPUS:0037085255
VL - 277
SP - 4601
EP - 4604
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 7
ER -