Synaptotagmin VII as a plasma membrane Ca2+ sensor in exocytosis
Synaptotagmin VII as a plasma membrane Ca2+ sensor in exocytosis
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DOI：
10.1016/s0896-6273(01)00290-2
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发表时间：
2001-05-01
期刊：
影响因子：
16.2
通讯作者：
Südhof, TC
中科院分区：
文献类型：
--
作者：
Sugita, S;Han, WP;Südhof, TC
突触素I和II是突触囊泡的钙结合蛋白，对钙离子触发的神经递质的快速释放是必不可少的。然而，缺乏这些突触的中枢性突触和神经内分泌细胞仍然表现出钙离子诱发的胞吐作用。我们现在提出，突触凝集素VII在突触胞吐作用中起质膜钙感受器的作用，与囊泡突触凝集蛋白互补。我们发现，突触素VII的选择性剪接形式在大脑中以发育调节的模式表达，并集中在中央突触的突触前活动区。在神经内分泌PC12细胞中，突触素VII的C(2)A和C2B结构域是钙依赖的胞吐作用的有效抑制者，但只有当它们与钙离子结合时，我们的数据表明，在突触小泡的胞吐中，不同的突触凝集素作为两个融合伙伴、质膜(突触凝集素VII)和突触小泡(突触聚集素I和II)上的独立钙感受器发挥作用。
Synaptotagmins I and II are Ca2+ binding proteins of synaptic vesicles essential for fast Ca2+-triggered neurotransmitter release. However, central synapses and neuroendocrine cells lacking these synaptotagmins still exhibit Ca2+-evoked exocytosis. We now propose that synaptotagmin VII functions as a plasma membrane Ca2+ sensor in synaptic exocytosis complementary to vesicular synaptotagmins. We show that alternatively spliced forms of synaptotagmin VII are expressed in a developmentally regulated pattern in brain and are concentrated in presynaptic active zones of central synapses. In neuroendocrine PC12 cells, the C(2)A and C2B domains of synaptotagmin VII are potent inhibitors of Ca2+-dependent exocytosis, but only when they bind Ca2+, Our data suggest that in synaptic vesicle exocytosis, distinct synaptotagmins function as independent Ca2+ sensors on the two fusion partners, the plasma membrane (synaptotagmin VII) versus synaptic vesicles (synaptotagmins I and II).