Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
Curr Opin Neurobiol. 2010 Oct;20(5):563-71. doi: 10.1016/j.conb.2010.05.007. Epub 2010 Jun 25.
The classical roles of α(2)δ proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane topology, but we find that they can form GPI-anchored proteins. Moreover α(2)δ-1 and α(2)δ-3 have been shown to have novel functions in synaptogenesis, independent of their effect on calcium channels. In neurons, the α(2)δ-1 subunits are present mainly in presynaptic terminals. Peripheral sensory nerve injury results in the up-regulation of α(2)δ-1 in dorsal root ganglion (DRG) neurons, and there is a consequent increase in trafficking of α(2)δ-1 to their terminals. Furthermore, gabapentinoid drugs, which bind to α(2)δ-1 and α(2)δ-2, not only impair their trafficking, but also affect α(2)δ-1-dependent synaptogenesis. These drugs may interfere with α(2)δ function at several different levels.
α(2)δ 蛋白的经典作用是作为辅助钙通道亚基，增强通道运输。它们被认为具有 I 型跨膜拓扑结构，但我们发现它们可以形成 GPI 锚定蛋白。此外，α(2)δ-1 和 α(2)δ-3 已被证明在突触发生中具有新的功能，与其对钙通道的影响无关。在神经元中，α(2)δ-1 亚基主要存在于突触前末端。周围感觉神经损伤导致背根神经节 (DRG) 神经元中 α(2)δ-1 的上调，并且随之增加 α(2)δ-1 向其末端的运输。此外，gabapentinoid 类药物与 α(2)δ-1 和 α(2)δ-2 结合，不仅会损害它们的运输，还会影响 α(2)δ-1 依赖性突触发生。这些药物可能在几个不同的水平上干扰 α(2)δ 的功能。
