Deciphering the role of water channel aquaporin-4 in muscle and brain

破译水通道aquaporin-4在肌肉和大脑中的作用

• 批准号: RGPIN-2017-05852
• 负责人: Yokota, Toshifumi
• 金额: $ 2.04万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629196
• 关键词: Deciphering; role; water; channel; aquaporin

Water channels called aquaporins (AQPs) are membrane proteins that conduct water molecules in and out of the cell. AQP4 is selectively expressed at the muscle membrane of fast twitch (type II) fibres, and one of the most abundant proteins in human brain. However, its roles in muscle and brain have remained elusive. We previously identified that AQP4 is localized by alpha-syntrophin at the cell membrane in muscle and brain (Yokota et al. 2000). More recently, we have shown that alpha-syntrophin deficient muscles exhibit impaired muscle volume regulation and muscle force recovery after osmotic shocks or treadmill exercise (Yokota et al. 2014, Nichols et al. 2015). We hypothesize that 1) AQP4 plays important roles in recovery from muscle fatigue during and after exercise, and 2) AQP4 is involved in increased cerebrospinal fluid (CSF) flow during and after exercise. The goal of this study is to decipher novel roles of AQP4 by analyzing mutant mouse models.

被称为水通道蛋白（AQPs）的水通道是引导水分子进出细胞的膜蛋白。AQP4选择性表达于快抽动（II型）纤维的肌膜，是人脑中最丰富的蛋白质之一。然而，它在肌肉和大脑中的作用仍然难以捉摸。我们之前发现AQP4通过α -syntrophin定位于肌和脑的细胞膜（Yokota et al. 2000）。最近，我们发现α -syntrophin缺乏的肌肉在渗透冲击或跑步机运动后表现出肌肉体积调节和肌肉力量恢复受损（Yokota et al. 2014, Nichols et al. 2015）。我们推测1)AQP4在运动中和运动后肌肉疲劳恢复中起重要作用，2)AQP4参与运动中和运动后脑脊液（CSF）流量增加。本研究的目的是通过分析突变小鼠模型来破译AQP4的新作用。