We are grateful to Gaku Sakaguchi for the gift of the antibody and Dr. Masakazu Hatanaka for encouragement during this study. We also thank Dr. Harukazu Suzuki for helpful discussions and Dr. Osamu Yoshie for critical reading of the manuscript.

  • 1
    Bear M.F. & Malenka R.C. (1994) Synaptic plasticity : LTP and LTD.Curr. Opin. Neurobiol. 4,389399.
  • 2
    Ben-Ari Y. & Represa A. (1990) Brief seizure episodes induce long-term potentiation and mossy fibre sprouting in the hippocampus.Trends Neurosci. 13,312318.
  • 3
    Bliss T.V. & Collingridge G.L. (1993) A synaptic model of memory : long-term potentiation in the hippocampus.Nature 361,3139.
  • 4
    Brennan P., Kaba H., Keverne E.B. (1990) Olfactory recognition : a simple memory system.Science 250,12231226.
  • 5
    Brose N., Hofmann K., Hata Y., Südhof T.C. (1995) Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of Ca2+-domain proteins. J. Biol. Chem. 270,2527325280.
  • 6
    Chapman E.R., Hanson P.I., An S., Jahn R. (1995) Ca2+ regulates the interaction between synaptotagmin and syntaxin. 1.J. Biol. Chem. 270,2366723671.
  • 7
    Creutz C.E., Tomsig J.L., Snyder S.L., Gautier M.C., Skouri F., Beisson J., Cohen J. (1998) The copines, a novel class of C2 domain-containing, calcium dependent, phospholipid-binding proteins conserved from paramecium to humans.J. Biol. Chem. 273,13931402.
  • 8
    Fukuda M., Aruga J., Niinobe M., Aimoto S., Mikoshiba K. (1994) Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II.J. Biol. Chem. 269,2920629211.
  • 9
    Geppert M., Goda Y., Hammer R.E., Li C., Rosahl T.W., Stevens C.F., Südhof T.C. (1994) Synaptotagmin I : a major Ca2+ sensor for transmitter release at a central synapse.Cell 79,717727.
  • 10
    Johnston P.A., Archer B.T.D., Robinson K., Mignery G.A., Jahn R., Südhof T.C. (1991) rab3A attachment to the synaptic vesicle membrane mediated by a conserved polyisoprenylated carboxyterminal sequence.Neuron 7,101109.
  • 11
    Kaba H. & Nakanishi S. (1995) Synaptic mechanisms of olfactory recognition memory.Rev. Neurosci. 6,125141.
  • 12
    Kuwajima G., Futatsugi A., Niinobe M., Nakanishi S., Mikoshiba K. (1992) Two types of ryanodine receptors in mouse brain : skeletal muscle type exclusively in Purkinje cells and cardiac muscle type in various neurons.Neuron 9,11331142.
  • 13
    Laemmli U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage. T4.Nature 227,680685.
  • 14
    Li C., Takei K., Geppert M., Daniell L., Stenius K., Chapman E.R., Jahn R., De Camilli P., Südhof T.C. (1994) Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C. Neuron 13,885898.
  • 15
    Marqueze B., Boudier J.A., Mizuta M., Inagaki N., Seino S., Seagar M. (1995) Cellular localization of synaptotagmin I, II, and III mRNAs in the central nervous system and pituitary and adrenal glands of the rat.J. Neurosci. 15,49064917.
  • 16
    Nakayama M., Miyake T., Gahara Y., Ohara O., Kitamura T. (1995) A novel RING-H2 motif protein downregulated by axotomy : its characteristic localization at the postsynaptic density of axosomatic response.J. Neurosci. 15,52385248.
  • 17
    Nakayama T., Yaoi T., Yasui M., Kuwajima G. (1998) N-Copine : a novel two C2-domain-containing protein with neuronal activity-regulated expression. FEBS Lett. 428,8084.
  • 18
    Nishizuka Y. (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion.Nature 308,693698.
  • 19
    Orita S., Sasaki T., Naito A., Komuro R., Ohtsuka T., Maeda M., Suzuki H., Igarashi H., Takai Y. (1995) Doc2 : a novel brain protein having two repeated C2-like domains.Biochem. Biophys. Res. Commun. 206,439448.
  • 20
    Orita S., Sasaki T., Komuro R., Sakaguchi G., Maeda M., Igarashi H., Takai Y. (1996) Doc2 enhances Ca2+-dependent exocytosis from PC12 cells. J. Biol. Chem. 271,72577260.
  • 21
    Sakaguchi G., Orita S., Maeda M., Igarashi H., Takai Y. (1995) Molecular cloning of an isoform of Doc2 having two C2-like domains.Biochem. Biophys. Res. Commun. 217,10531061.DOI: 10.1006/bbrc.1995.2876
  • 22
    Schiavo G., Stenbeck G., Rothman J.E., Sollner T.H. (1997) Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses.Proc. Natl. Acad. Sci USA 94,9971001.
  • 23
    Shao X., Davletov B.A., Sutton R.B., Südhof T.C., Rizo J. (1996) Bipartite Ca2+ -binding motif in C2 domains of synaptotagmin and protein kinase. C.Science 273,248251.
  • 24
    Sheng Z.H., Rettig J., Takahashi M, Catterall W.A. (1994) Identification of a syntaxin-binding site on N-type calcium channels.Neuron 13,13031313.
  • 25
    Shirataki H., Kaibuchi K, S, Kishida S., Yamaguchi T., Wada K., Miyazaki M., Takai Y. (1993) Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin.Mol. Cell. Biol..13,20612068.
  • 26
    Südhof T.C. & Rizo J. (1996) Synaptotagmins : C2-domain proteins that regulate membrane traffic.Neuron 17,379388.
  • 27
    Sugita S., Hata Y., Südhof T.C. (1996) Distinct Ca(2+)-dependent properties of the first and second C2-domains of synaptotagmin. I.J. Biol. Chem..271,12621265.
  • 28
    Ullrich B., Li C., Zhang J.Z., McMahon H., Anderson R.G., Geppert M., Südhof T.C. (1994) Functional properties of multiple synaptotagmins in brain.Neuron 13,12811291.