Sugita S, Khvochtev M, Südhof T C
Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
Neuron. 1999 Mar;22(3):489-96. doi: 10.1016/s0896-6273(00)80704-7.
Alpha-latrotoxin is a potent neurotoxin that triggers synaptic exocytosis. Surprisingly, two distinct neuronal receptors for alpha-latrotoxin have been described: CIRL/latrophilin 1 (CL1) and neurexin-1alpha. Alpha-latrotoxin is thought to trigger exocytosis by binding to CL1, while the role of neurexin 1alpha is uncertain. Using PC12 cells, we now demonstrate that neurexins indeed function as alpha-latrotoxin receptors that are at least as potent as CL1. Both alpha- and beta-neurexins represent autonomous alpha-latrotoxin receptors that are regulated by alternative splicing. Similar to CL1, truncated neurexins without intracellular sequences are fully active; therefore, neurexins and CL1 recruit alpha-latrotoxin but are not themselves involved in exocytosis. Thus, alpha-latrotoxin is unique among neurotoxins, because it utilizes two unrelated receptors, probably to amplify recruitment of alpha-latrotoxin to active sites.
α-拉曲毒素是一种能引发突触胞吐作用的强效神经毒素。令人惊讶的是，已经发现了两种不同的α-拉曲毒素神经元受体：CIRL/拉曲亲和素1（CL1）和神经连接蛋白-1α。据认为，α-拉曲毒素通过与CL1结合来触发胞吐作用，而神经连接蛋白1α的作用尚不确定。我们利用PC12细胞，现在证明神经连接蛋白确实作为α-拉曲毒素受体发挥作用，其效力至少与CL1相同。α-神经连接蛋白和β-神经连接蛋白都是通过可变剪接调控的自主α-拉曲毒素受体。与CL1类似，没有细胞内序列的截短神经连接蛋白具有完全活性；因此，神经连接蛋白和CL1能募集α-拉曲毒素，但它们本身并不参与胞吐作用。因此，α-拉曲毒素在神经毒素中是独特的，因为它利用两种不相关的受体，可能是为了增强α-拉曲毒素向活性位点的募集。
