Water Permeability of Aquaporin-4 Channel Depends on Bilayer Composition, Thickness, and Elasticity
Water Permeability of Aquaporin-4 Channel Depends on Bilayer Composition, Thickness, and Elasticity
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DOI：
10.1016/j.bpj.2012.09.025
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发表时间：
2012-11-07
影响因子：
3.4
通讯作者：
McIntosh, Thomas J.
中科院分区：
文献类型：
--
作者：
Tong, Jihong;Briggs, Margaret M.;McIntosh, Thomas J.
水通道蛋白-4（AQP 4）是哺乳动物脑中的主要水通道，在星形胶质细胞中特别丰富，其质膜通常含有高浓度的胆固醇。在这里，我们测试的假设，水的渗透性的两个天然存在的亚型（AQP 4-M1和AQP 4-M23）取决于双层的机械/结构特性调节胆固醇和磷脂的组合物。使用含有AQP 4和三种不同脂质混合物的蛋白脂质体进行渗透应力测量：1）磷脂酰胆碱（PC）和磷脂酰甘油（PG）; 2）PC，PG，含40 mol%胆固醇;和3）鞘磷脂（SM），PG，含40 mol %胆固醇。在PC：PG、PC：PG：胆固醇和SM：PG：胆固醇中，AQP 4-M1的单位渗透率分别为3.3 +/- 0.4 x 10（-13）cm（3）/s（平均值+/- SE）、1.2 +/-0.1 x 10（-13）cm（3）/s和0.4 +/- 0.1 x 10（-13）cm（3）/s。在PC：PG、PC：PG：胆固醇和SM：PG：胆固醇中，AQP 4-M23的单位渗透率分别为2.1 +/-0.2 x 10（-13）cm（3）/s、0.8 +/-0.1 x 10（-13）cm（3）/s和0.3 +/- 0.1 x 10（-13）cm（3）/s。因此，对于每个异构体的单位渗透率强烈依赖于双层组合物，并系统地减少与增加双层压缩模量和双层厚度。这些观察结果表明，改变脂质环境提供了一种调节水通道渗透性的手段。这种渗透性变化可能具有生理后果，因为AQP 4水渗透性将通过其螯合到SM中而降低：富含胆固醇的筏微区。相反，在缺血条件下，星形胶质细胞膜胆固醇含量降低，这可能增加AQP 4渗透性。
Aquaporin-4 (AQP4) is the primary water channel in the mammalian brain, particularly abundant in astrocytes, whose plasma membranes normally contain high concentrations of cholesterol. Here we test the hypothesis that the water permeabilities of two naturally occurring isoforms (AQP4-M1 and AQP4-M23) depend on bilayer mechanical/structural properties modulated by cholesterol and phospholipid composition. Osmotic stress measurements were performed with proteoliposomes containing AQP4 and three different lipid mixtures: 1), phosphatidylcholine (PC) and phosphatidylglycerol (PG); 2), PC, PG, with 40 mol% cholesterol; and 3), sphingomyelin (SM), PG, with 40 mol % cholesterol. The unit permeabilities of AQP4-M1 were 3.3 +/- 0.4 x 10(-13) cm(3)/s (mean +/- SE), 1.2 +/- 0.1 x 10(-13) cm(3)/s, and 0.4 +/- 0.1 x 10(-13) cm(3)/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. The unit permeabilities of AQP4-M23 were 2.1 +/- 0.2 x 10(-13) cm(3)/s, 0.8 +/- 0.1 x 10(-13) cm(3)/s, and 0.3 +/- 0.1 x 10(-13) cm(3)/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. Thus, for each isoform the unit permeabilities strongly depended on bilayer composition and systematically decreased with increasing bilayer compressibility modulus and bilayer thickness. These observations suggest that altering lipid environment provides a means of regulating water channel permeability. Such permeability changes could have physiological consequences, because AQP4 water permeability would be reduced by its sequestration into SM:cholesterol-enriched raft microdomains. Conversely, under ischemic conditions astrocyte membrane cholesterol content decreases, which could increase AQP4 permeability.