Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this balance is associated with several diseases, such as Liddle’s and long QT syndromes. Because of the vital role of these proteins in human health and disease, knowledge of ICh turnover is essential. Clathrin-dependent and -independent mechanisms have been the primary mechanisms identified with ICh endocytosis and degradation. Several molecular determinants recognized by the cellular internalization machinery have been discovered. Moreover, specific conditions can trigger the endocytosis of many IChs, such as the activation of certain receptors, hypokalemia, and some drugs. Ligand-dependent receptor activation primarily results in the posttranslational modification of IChs and the recruitment of important mediators, such as β-arrestins and ubiquitin ligases. However, endocytosis is not a final fate. Once internalized into endosomes, IChs are either sorted to lysosomes for degradation or recycled back to the plasma membrane. Rab proteins are crucial participants during these turnover steps. In this review, we describe the major ICh endocytic pathways, the signaling inputs triggering ICh internalization, and the key mediators of this essential cellular process.

中文翻译：

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胞吞作用：控制离子通道功能的周转机制。

离子通道（IChs）是跨膜蛋白，可选择性地驱动离子穿过膜。IChs的功能部分取决于它们的丰度和在细胞中的适当位置，并通过分泌，内吞和降解途径之间的微妙平衡进行微调。这种平衡的破坏与多种疾病有关，例如里德尔氏病和长QT综合征。由于这些蛋白质在人类健康和疾病中的重要作用，因此了解ICh转换至关重要。网格蛋白依赖性和非依赖性机制已被鉴定为ICh内吞和降解的主要机制。已经发现了细胞内在化机制认可的几种分子决定簇。此外，特定条件可能会触发许多ICh的内吞作用，例如某些受体的激活，低血钾，和一些药物。配体依赖性受体激活主要导致IChs的翻译后修饰和重要介体（如β-arrestin和泛素连接酶）的募集。然而，胞吞作用并不是最终的命运。一旦内化到内体中，ICh要么被分类为溶酶体以进行降解，要么被循环回到质膜。在这些周转步骤中，Rab蛋白是至关重要的参与者。在这篇综述中，我们描述了主要的ICh细胞内吞途径，触发ICh内在化的信号输入以及这一基本细胞过程的关键介体。一旦内化到内体中，ICh要么被分类为溶酶体以进行降解，要么被循环回到质膜。在这些周转步骤中，Rab蛋白是至关重要的参与者。在这篇综述中，我们描述了主要的ICh细胞内吞途径，触发ICh内在化的信号输入以及这一基本细胞过程的关键介体。一旦内化到内体中，ICh要么被分类为溶酶体以进行降解，要么被循环回到质膜。在这些周转步骤中，Rab蛋白是至关重要的参与者。在这篇综述中，我们描述了主要的ICh内吞途径，触发ICh内在化的信号输入以及这一基本细胞过程的关键介体。