The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2021-06-10 , DOI: 10.1007/s00232-021-00184-z Vitalii Kryvenko 1, 2 , Olga Vagin 3, 4 , Laura A Dada 5 , Jacob I Sznajder 5 , István Vadász 1, 2
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Abstract
The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions.
Graphic Abstract
中文翻译：
健康和疾病中内质网 Na,K-ATP 酶的成熟
摘要
Na,K-ATPase 通过驱动 Na +和 K +的主动交换来建立细胞的电化学梯度消耗 ATP 时的离子。最小功能性转运蛋白由催化性α-亚基和具有伴侣活性的β-亚基组成。Na,K-ATPase 还作为细胞粘附分子发挥作用并参与各种细胞内信号通路。Na,K-ATP 酶的成熟和运输包括内质网 (ER) 和高尔基体中酶的共翻译和翻译后加工以及随后递送至质膜 (PM)。酶的 ER 折叠被认为是蛋白质膜递送的限速步骤。已经证明，只有组装好的 Na,K-ATPase α:β-复合物可以离开细胞器，而未组装、错误折叠或未折叠的亚基保留在 ER 中并随后被降解。Na,K-ATP酶的功能丧失与肺有关，心脏、肾脏和神经系统疾病。最近，已经表明 ER 功能障碍，特别是细胞器稳态的改变，以及 ER 驻留分子伴侣活性受损可能会阻碍 Na，K-ATP 酶亚基的折叠，从而降低酶的丰度和功能。在下午。在这里，我们总结了我们目前对生理和病理生理条件下 ER 中 Na、K-ATP 酶的成熟和后续加工的理解。
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