来源：生物谷 2012-05-15 09:08
近日，Nature上的一项新研究发现一蛋白质能控制神经递质，研究结果可能有助于设计开发新的药物，以改善脑细胞之间的沟通、有效治疗神经系统疾病。
近日，威尔康乃尔医学院的科学家发现，单蛋白质--alpha 2 delta具有控制神经递质和其他突触大脑神经元之间交流的化学物质的体积流量。这项研究发表在Nature杂志上，研究揭示了脑细胞如何通过这些信号彼此交流、传达思想、感情和行动，其中alpha 2 delta起到了至关重要的作用。
在这项研究中，研究人员还提示了止痛药Lyrica是如何发挥作用，alpha 2 delta是这种药物的靶标。
研究人员发现，alpha 2 delta决定了多少钙离子通道神经元之间的突触。触发进入这些渠道中的钙进入突触的化学信号传输，所以传输体积和神经传导速度取决于这些通道的可用性。
研究人员发现，去除alpha 2 delta抑制了脑细胞突触通过钙离子通道获得钙。 但是，如果你过度alpha 2 delta的话，突触间通道数增了加两倍的。
在此之前的研究，Lyrica结合alpha 2 delta是神经性疼痛、癫痫和纤维肌痛的有效药物，但很少有人理解这种蛋白质工程是如何控制突触的。（生物谷：Bioon.com）
α2δ expression sets presynaptic calcium channel abundance and release probability
Michael B. Hoppa,Beatrice Lana,Wojciech Margas,Annette C. Dolphin& Timothy A. Ryan
Synaptic neurotransmitter release is driven by Ca2+ influx through active zone voltage-gated calcium channels (VGCCs)1, 2. Control of active zone VGCC abundance and function remains poorly understood. Here we show that a trafficking step probably sets synaptic VGCC levels in rats, because overexpression of the pore-forming α1A VGCC subunit fails to change synaptic VGCC abundance or function. α2δs are a family of glycosylphosphatidylinositol (GPI)-anchored VGCC-associated subunits3 that, in addition to being the target of the potent neuropathic analgesics gabapentin and pregabalin (α2δ-1 and α2δ-2)4, 5, were also identified in a forward genetic screen for pain genes (α2δ-3)6. We show that these proteins confer powerful modulation of presynaptic function through two distinct molecular mechanisms. First, α2δ subunits set synaptic VGCC abundance, as predicted from their chaperone-like function when expressed in non-neuronal cells3, 7. Second, α2δs configure synaptic VGCCs to drive exocytosis through an extracellular metal ion-dependent adhesion site (MIDAS), a conserved set of amino acids within the predicted von Willebrand A domain of α2δ. Expression of α2δ with an intact MIDAS motif leads to an 80% increase in release probability, while simultaneously protecting exocytosis from blockade by an intracellular Ca2+ chelator. α2δs harbouring MIDAS site mutations still drive synaptic accumulation of VGCCs; however, they no longer change release probability or sensitivity to intracellular Ca2+ chelators. Our data reveal dual functionality of these clinically important VGCC subunits, allowing synapses to make more efficient use of Ca2+ entry to drive neurotransmitter release.
Nature：脑脊髓液测试可追踪某些脑瘤中的疾病进展
APP专享
Nature：源自人肠道微生物组的共生菌混合物诱导抗肿瘤免疫反应
APP专享
Nature：细菌代谢物对肠道免疫反应产生重大影响
APP专享
Nature：惊人大翻转！自噬并不促进癌症，相反将癌症扼杀于摇篮之中
APP专享
内含子并非垃圾DNA！两篇Nature揭示它们具有惊人的稳定性和功能
APP专享
Nature：重磅！首次成功地在哺乳动物中进行基因驱动
APP专享
Nature：发现靶向杯状病毒的新靶标
APP专享
QB 期刊 | 近天然蛋白质结构“新选择”
APP专享
研究揭示蛋白质SUMO化修饰精细调控植物次生细胞壁增厚新机制
APP专享
Nature医学：新型标志物或提早16年检出阿尔茨海默症
APP专享
空中讲坛 Webinar
