Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins (original) (raw)

Nature volume 375, pages 594–599 (1995)Cite this article

Abstract

SYNAPTOTAGMINS (Syts) are brain-specific Ca2+/phospholipidbinding proteins1–5. In hippocampal synapses, Syt I is essential for fast Ca2+-dependent synaptic vesicle exocytosis but not for Ca2 +- independent exocytosis3. In vertebrates and invertebrates6–9, Syt may therefore participate in Ca22 +–dependent synaptic membrane fusion, either by serving as the Ca2 + sensor in the last step of fast Ca2 +-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 = 3–6µM) than those required for exocytosis12. Furthermore, Syts bind clathrin–AP2 with high affinity, indicating that they may play a general role in endocytosis4,5 rather than being confined to a specialized function in regulated exocytosis3. 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 = 0.1–1.0nM) 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 Ca2+–concentration dependence (EC50 = 3–6µM). The same C2 domains also bind syntaxin as a function of Ca2 + but the Ca2 +–concentration dependence of Syt I, II and V (>200 µM) differs from that of Syt III and VII (<10 µM). Syts therefore appear to be ubiquitous proteins with a role in exocytosis mediated by syntaxin binding. The Ca2 +levels needed to trigger syntaxin binding by the different Syts suggest that they play distinct roles in membrane fusion; the level required by Syt I approximates those required for synaptic exocytosis.

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Authors and Affiliations

  1. Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA
    Cai Li, Beate Ullrich, Nils Brose & Thomas C. Südhof
  2. Departments of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA
    Jimmy Z. Zhang & Richard G. W. Anderson
  3. Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA
    Thomas C. Südhof

Authors

  1. Cai Li
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  2. Beate Ullrich
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  3. Jimmy Z. Zhang
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  4. Richard G. W. Anderson
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  5. Nils Brose
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  6. Thomas C. Südhof
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Li, C., Ullrich, B., Zhang, J. et al. Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins.Nature 375, 594–599 (1995). https://doi.org/10.1038/375594a0

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