Ullrich B, Li C, Zhang J Z, McMahon H, Anderson R G, Geppert M, Südhof T C
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Neuron. 1994 Dec;13(6):1281-91. doi: 10.1016/0896-6273(94)90415-4.
At least four forms of synaptotagmin are expressed in neurons. Of these, synaptotagmin I has an essential function in mediating Ca(2+)-triggered neurotransmitter release at hippocampal synapses, but the functional implications of multiple synaptotagmins are unknown. Synaptotagmins I-III exhibit a strikingly differential distribution between synapses, with most neurons coexpressing either synaptotagmins I or II with III. Synaptotagmin IV is present uniformly throughout the brain at low levels. Synaptotagmins III and IV are both coexpressed with synaptotagmin I in hippocampal synapses, suggesting that these synaptotagmins are not functionally redundant. The first C2 domains of synaptotagmins I-III exhibit similar Ca2+ affinities in phospholipid-binding assays, whereas that of synaptotagmin IV is unable to bind Ca2+. All synaptotagmins tested bind the clathrin-adaptor protein AP-2 with high affinity. Our results suggest that different synaptotagmins serve distinct but overlapping functions in neuronal membrane traffic, with synaptotagmins I and II representing alternative Ca2+ sensors in exocytosis and all synaptotagmins functioning as AP-2 receptors in endocytosis.
神经元中至少表达四种形式的突触结合蛋白。其中，突触结合蛋白I在介导海马突触处Ca(2+)触发的神经递质释放中具有重要功能，但多种突触结合蛋白的功能意义尚不清楚。突触结合蛋白I - III在突触之间表现出显著的差异分布，大多数神经元共表达突触结合蛋白I或II与III。突触结合蛋白IV在整个大脑中均匀分布，但水平较低。突触结合蛋白III和IV在海马突触中均与突触结合蛋白I共表达，这表明这些突触结合蛋白在功能上并非冗余。在磷脂结合试验中，突触结合蛋白I - III的第一个C2结构域表现出相似的Ca2+亲和力，而突触结合蛋白IV的第一个C2结构域则无法结合Ca2+。所有测试的突触结合蛋白都以高亲和力结合网格蛋白衔接蛋白AP - 2。我们的结果表明，不同的突触结合蛋白在神经元膜运输中发挥着不同但重叠的功能，突触结合蛋白I和II代表胞吐作用中的替代性Ca2+传感器，而所有突触结合蛋白在内吞作用中均作为AP - 2受体发挥作用。
