Ca(2+)-dependent and -Independent Activities of Neural and Non-Neural Synaptotagmins

Nature. 1995 Jun 15;375(6532):594-9. doi: 10.1038/375594a0.

Abstract

Synaptotagmins (Syts) are brain-specific Ca2+/phospholipid-binding proteins. In hippocampal synapses, Syt I is essential for fast Ca(2+)-dependent synaptic vesicle exocytosis but not for Ca(2+)-independent exocytosis. In vertebrates and invertebrates, Syt may therefore participate in Ca(2+)-dependent synaptic membrane fusion, either by serving as the Ca2+ sensor in the last step of fast Ca(2+)-triggered neurotransmitter release, or by collaborating with an additional Ca2+ sensor. While Syt I binds Ca2+ (refs 10, 11), its phospholipid binding is triggered at lower calcium concentrations (EC50 = 3-6 microM) than those required for exocytosis. Furthermore, Syts bind clathrin-AP2 with high affinity, indicating that they may play a general role in endocytosis rather than being confined to a specialized function in regulated exocytosis. Here we resolve this apparent contradiction by describing four Syts, three of which (Syt VI, VII and VIII) are widely expressed in non-neural tissues. All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins. The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids with a similar Ca(2+)-concentration dependence (EC50 = 3-6 microM). The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs from that of Syt III and VII (< 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Calcium / metabolism*
  • Calcium-Binding Proteins*
  • Cell Line
  • Cloning, Molecular
  • Exocytosis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Protein Binding
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Rats
  • Recombinant Proteins / metabolism
  • Synapses / metabolism
  • Synaptosomal-Associated Protein 25
  • Synaptotagmins

Substances

  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Recombinant Proteins
  • SYT3 protein, human
  • SYT6 protein, human
  • SYT8 protein, human
  • Snap25 protein, mouse
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Synaptotagmins
  • Calcium

Associated data

  • GENBANK/U20105
  • GENBANK/U20106
  • GENBANK/U20107
  • GENBANK/U20108
  • GENBANK/U20109
  • GENBANK/U20110