Mints as adaptors -: Direct binding to neurexins and recruitment of Munc18
Mints as adaptors -: Direct binding to neurexins and recruitment of Munc18
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DOI：
10.1074/jbc.c000656200
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发表时间：
2000-12-22
影响因子：
4.8
通讯作者：
Südhof, TC
中科院分区：
文献类型：
--
作者：
Biederer, T;Südhof, TC
Mint1 (X11/人 Lin-10) 和 Mint2 是与 Munc18-1 (n/rb-sec1) 结合的神经元衔接蛋白，Munc18-1 (n/rb-sec1) 是突触小泡胞吐作用所必需的蛋白质。 Mint1 之前已在与 CASK 的复合物中进行了表征，CASK 是另一种接头蛋白，反过来又与神经毒素相互作用。神经毒素是神经元特异性细胞表面蛋白，充当兴奋性神经毒素 CW-latrotoxin 的受体。因此，Mint1 的一个可能功能是介导 Munc18 向神经毒素的募集。与这一假设一致，我们现在表明神经毒素的细胞质尾部通过涉及 Mint1 的多蛋白复合物捕获 Munc18。此外，我们证明 Mint1 和 Mint2 都可以在 PDZ 结构域介导的相互作用中直接与神经毒素结合。各种含有 Mint 和/或 CASK 的复合物可以在神经毒素上组装，并且我们证明 Mint1 可以同时结合 Munc18 和 CASK。我们的数据支持一个模型，其中 Mints 的功能之一是将囊泡融合蛋白 Munc18 定位到质膜上由神经毒素定义的位点，大概在胞吐作用点附近。
Mint1 (X11/human Lin-10) and Mint2 are neuronal adaptor proteins that bind to Munc18-1 (n/rb-sec1), a protein essential for synaptic vesicle exocytosis. Mint1 has previously been characterized in a complex with CASK, another adaptor protein that in turn interacts with neurexins. Neurexins are neuron-specific cell surface proteins that act as receptors for the excitatory neurotoxin cw-latrotoxin. Hence, one possible function for Mint1 is to mediate the recruitment of Munc18 to neurexins. In agreement with this hypothesis, we now show that the cytoplasmic tail of neurexins captures Munc18 via a multiprotein complex that involves Mint1. Furthermore, we demonstrate that both Mint1 and Mint2 can directly bind to neurexins in a PDZ domain-mediated interaction. Various Mint and/or CASK-containing complexes can be assembled on neurexins, and we demonstrate that Mint1 can bind to Munc18 and CASK simultaneously. Our data support a model whereby one of the functions of Mints is to localize the vesicle fusion protein Munc18 to those sites at the plasma membrane that are defined by neurexins, presumably in the vicinity of points of exocytosis.