Close membrane-membrane proximity induced by Ca2+-dependent multivalent binding of synaptotagmin-1 to phospholipids
Close membrane-membrane proximity induced by Ca2+-dependent multivalent binding of synaptotagmin-1 to phospholipids
复制标题
DOI：
10.1038/nsmb1056
复制
发表时间：
2006-03-01
影响因子：
16.8
通讯作者：
Rizo, J
中科院分区：
文献类型：
--
作者：
Araç, D;Chen, XC;Rizo, J
Synaptotagmin通过其两个C-2结构域在神经递质释放中作为Ca2+传感器。Ca2+依赖性磷脂结合是synaptotagmin功能的关键，但目前尚不清楚这种活性如何与参与释放的SNARE复合物合作，或者为什么Ca2+结合到C2B结构域比Ca2+结合到C(2)A结构域对释放更重要。在这里，我们表明Ca2+诱导突触蛋白的高亲和力同时结合到两个膜，使它们接近。synaptotagmin C2B结构域足以实现这种能力，这源于其表面周围丰富的碱性残基。我们提出了一个模型，其中synaptotagmin与SNAREs合作，将突触囊泡和质膜结合在一起，并通过其C2B结构域的高度正静电电位加速膜融合。
Synaptotagmin acts as a Ca2+ sensor in neurotransmitter release through its two C-2 domains. Ca2+-dependent phospholipid binding is key for synaptotagmin function, but it is unclear how this activity cooperates with the SNARE complex involved in release or why Ca2+ binding to the C2B domain is more crucial for release than Ca2+ binding to the C(2)A domain. Here we show that Ca2+ induces high-affinity simultaneous binding of synaptotagmin to two membranes, bringing them into close proximity. The synaptotagmin C2B domain is sufficient for this ability, which arises from the abundance of basic residues around its surface. We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C2B domain.