Lao G, Scheuss V, Gerwin C M, Su Q, Mochida S, Rettig J, Sheng Z H
Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4154, USA.
Neuron. 2000 Jan;25(1):191-201. doi: 10.1016/s0896-6273(00)80882-x.
Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduces neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibits synaptic transmission. These findings suggest that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis.
Syntaxin-1是突触小泡对接/融合机制的关键组成部分，它与VAMP/突触囊泡蛋白和SNAP-25形成SNARE复合体。鉴定调节SNARE复合体形成的蛋白质对于理解神经递质释放及其调节的分子机制至关重要。我们已经克隆并鉴定了一种名为syntaphilin的蛋白质，它在大脑中选择性表达。Syntaphilin与SNAP-25竞争结合Syntaxin-1，并通过吸收游离的Syntaxin-1来抑制SNARE复合体的形成。在培养的海马神经元中瞬时过表达syntaphilin可显著减少神经递质的释放。此外，将syntaphilin引入培养的突触前颈上神经节神经元可抑制突触传递。这些发现表明，syntaphilin可能作为一种分子钳，控制游离Syntaxin-1用于SNARE复合体组装的可用性，从而调节突触小泡的胞吐作用。
