LINGO1 is a transmembrane protein that is up-regulated in the cerebellum of patients with Parkinson's disease (PD) and Essential Tremor (ET). Patients with additional copies of the LINGO1 gene also present with tremor. Pharmacological or genetic ablation of large conductance Ca2+-activated K+ (BK) channels also result in tremor and motor disorders. We hypothesized that LINGO1 is a regulatory BK channel subunit. We show that 1) LINGO1 coimmunoprecipitated with BK channels in human brain, 2) coexpression of LINGO1 and BK channels resulted in rapidly inactivating BK currents, and 3) LINGO1 reduced the membrane surface expression of BK channels. These results suggest that LINGO1 is a regulator of BK channels, which causes a "functional knockdown" of these currents and may contribute to the tremor associated with increased LINGO1 levels.

中文翻译：

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LINGO1是大电导，Ca2 +激活的钾离子通道的调节亚基。

LINGO1是一种跨膜蛋白，在帕金森氏病（PD）和原发性震颤（ET）患者的小脑中表达上调。带有额外拷贝的LINGO1基因的患者也会出现震颤。大电导Ca2 +激活的K +（BK）通道的药理或遗传消融作用也会导致震颤和运动障碍。我们假设LINGO1是调节性BK通道亚基。我们显示1）LINGO1与人脑中的BK通道共免疫沉淀，2）LINGO1和BK通道的共表达导致BK电流快速失活，以及3）LINGO1减少BK通道的膜表面表达。这些结果表明，LINGO1是BK通道的调节剂，其导致这些电流的“功能性抑制”，并可能导致与LINGO1水平升高相关的震颤。