Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident protein, is regulated by dietary selenium and expressed at a relatively high level in neurons. SELENOK has been shown to participate in oxidation resistance, calcium (Ca²⁺) flux regulation, and the ER-associated degradation (ERAD) pathway in immune cells. However, its role in neurons has not been elucidated. Here, we demonstrated that SELENOK gene knockout markedly enhanced ER stress (ERS) and increased apoptosis in neurons. SELENOK gene knockout elicited intracellular Ca²⁺ flux and activated the m-calpain/caspase-12 cascade, thus inducing neuronal apoptosis both in vivo and in vitro. In addition, SELENOK knockout significantly reduced cognitive ability and increased anxiety in 7-month-old mice. Our findings reveal an unexpected role of SELENOK in regulating ERS-induced neuronal apoptosis.

硒蛋白 K (SELENOK) 是一种内质网 (ER) 驻留蛋白，受膳食硒的调节，并在神经元中以相对较高的水平表达。SELENOK 已被证明参与免疫细胞中的氧化抗性、钙 (Ca ²⁺ ) 通量调节和 ER 相关降解 (ERAD) 途径。然而，其在神经元中的作用尚未阐明。在这里，我们证明 SELENOK 基因敲除显着增强了内质网应激 (ERS) 并增加了神经元的凋亡。SELENOK 基因敲除引起细胞内 Ca ²⁺流动并激活m -calpain/caspase-12 级联，从而在体内和体外诱导神经元凋亡。此外，SELENOK 敲除显着降低了 7 个月大小鼠的认知能力并增加了焦虑。我们的研究结果揭示了 SELENOK 在调节 ERS ​​诱导的神经元凋亡中的意想不到的作用。