The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvβ1
The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvβ1
复制标题
DOI：
10.1016/j.neuron.2006.01.033
复制
发表时间：
2006-03-02
期刊：
影响因子：
16.2
通讯作者：
Fakler, B
中科院分区：
文献类型：
--
作者：
Schulte, U;Thumfart, JO;Fakler, B
电压门控钾 (Kv) 通道亚基 Kv1.1 是调节 CNS 神经元突触传递的突触前 A 型通道的主要组成部分。在这里，我们发现包含 Kv1.1 的通道与 Lgi1 复合，Lgi1 是富含亮氨酸的神经胶质瘤失活基因 1 (LGI1) 的功能未分配产物，它是常染色体显性形式的外侧颞叶癫痫 (ADILTE) 的病因。在海马结构中，Kv1.1 和 Lgi1 与轴突末端的 Kv1.4 和 Kv beta 1 共同组装。在由这些亚基组成的 A 型通道中，Lgi1 选择性地阻止 Kv beta 1 亚基介导的 N 型失活。相比之下，在 ADILTE 患者中发现的有缺陷的 Lgi1 分子无法发挥这种作用，导致通道具有快速失活动力学。结果确定 Lgi1 是 Kv1.1 相关蛋白复合物的一个新亚基，并表明突触前 A 型通道失活门控的变化可能促进癫痫活动。
The voltage-gated potassium (Kv) channel subunit Kv1.1 is a major constituent of presynaptic A-type channels that modulate synaptic transmission in CNS neurons. Here, we show that Kv1.1-containing channels are complexed with Lgi1, the functionally unassigned product of the leucine-rich glioma inactivated gene 1 (LGI1), which is causative for an autosomal dominant form of lateral temporal lobe epilepsy (ADILTE). In the hippocampal formation, both Kv1.1 and Lgi1 are coassembled with Kv1.4 and Kv beta 1 in axonal terminals. In A-type channels composed of these subunits, Lgi1 selectively prevents N-type inactivation mediated by the Kv beta 1 subunit. In contrast, defective Lgi1 molecules identified in ADILTE patients fall to exert this effect resulting in channels with rapid inactivation kinetics. The results establish Lgi1 as a novel subunit of Kv1.1-associated protein complexes and suggest that changes in inactivation gating of presynaptic A-type channels may promote epileptic activity.