Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.
Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.
复制标题
DOI：
10.1016/j.bbrc.2014.06.067
复制
发表时间：
2014-10-17
影响因子：
3.1
通讯作者：
Betenbaugh MJ
中科院分区：
文献类型：
--
作者：
Baycin-Hizal D;Gottschalk A;Jacobson E;Mai S;Wolozny D;Zhang H;Krag SS;Betenbaugh MJ
电压门控离子通道是调节细胞电兴奋性的跨膜蛋白，是神经、肌肉和心脏等电活性组织的重要组成部分。钾通道是最大的电压敏感通道亚族之一，也是研究最多的电压门控离子通道之一。电压门控通道可以被糖基化，糖基化模式的变化可以影响离子通道功能，导致神经和神经肌肉疾病以及先天性糖基化疾病 (CDG)。糖基化的改变也可以是后天获得的，并且似乎在发育和衰老中发挥作用。最近的研究集中在糖基化和唾液酸化对离子通道的影响，特别是电压门控钾和钠通道。唾液酸化的最终步骤通常影响通道激活和失活动力学。 O 或 N-聚糖上唾液酸的存在可以改变门控机制，并由于唾液酸的负电荷而导致电压传感域的构象变化。本手稿将概述唾液酸、钾和钠通道功能，以及唾液酸化对通道激活和失活的影响。
Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.