Regulation of eukaryotic aquaporins

Regulation of eukaryotic aquaporins
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真核水通道蛋白的调控

DOI:
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发表时间:
2016
期刊:
影响因子:
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通讯作者:
S. Törnroth
S. Törnroth
中科院分区:
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文献类型:
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作者:
M. Nyblom;S. Törnroth

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水通道蛋白(Aquaporins,AQP)是一种膜结合的水通道,它能促进水沿着渗透梯度穿过生物膜。由于所有活细胞都依赖于它们维持水平衡的能力,因此必须严格调节。在真核生物中,这是通过门控来实现的,门控涉及蛋白质的构象变化,从而物理地阻断水转运,或者通过运输来实现,其中AQP在细胞内储存位点和质膜之间穿梭。门控在植物水通道蛋白中是常见的,响应于环境胁迫,并已被证明是由磷酸化,pH值和二价阳离子的结合触发。已经证明了酵母水通道蛋白的门控作用,据信它可以保护酵母免受渗透压休克和快速冷冻。在哺乳动物中,AQP调节主要通过贩运实现。在人类中已经确定了13种AQP,其中大多数是通过对广泛刺激的贩运来调节的。最好表征的运输机制是肾脏集合管中的AQP 2,其在尿液浓缩中起关键作用。AQP 2的运输受垂体激素加压素的控制,加压素刺激AQP 2 C-末端的磷酸化,触发AQP 2从细胞内储存囊泡易位到顶端膜。人AQP的缺陷运输可导致几种疾病状态,例如肾源性尿崩症(AQP 2)和Sjogren综合征(AQP 5)。在这一章中,我们给出了一个概述,什么是已知的真核水通道蛋白的调节,特别是侧重于结构与功能的关系。我们讨论的生理作用,水通道蛋白的调节,具体的监管机制和重复发生的主题门控和贩运。(减)
Membrane-bound water channels known as aquaporins (AQPs) facilitate water transport across biological membranes along osmotic gradients. Since all living cells depend on their ability to maintain water homeostasis, this must be tightly regulated. In eukaryotes, this is achieved by gating, which involves a conformational change of the protein, thereby physically blocking water transport, or by trafficking in which AQPs are shuttled between intracellular storage sites and the plasma membrane. Gating is common amongst plant AQPs in response to environmental stress and has been shown to be triggered by phosphorylation, pH and binding of divalent cations. Gating has been demonstrated for yeast AQPs for which it is believed to confer protection against osmotic shock and rapid freezing. In mammals, AQP regulation is mainly achieved through trafficking. Thirteen AQPs have been identified in humans, the majority of which are regulated by trafficking in response to a wide range of stimuli. The far best characterized trafficking mechanism is that of AQP2 in the kidney collecting duct where it plays a key role in urine concentration. AQP2 trafficking is controlled by the pituitary hormone vasopressin that stimulates phosphorylation of the AQP2 C-terminus, triggering translocation of AQP2 from intracellular storage vesicles to the apical membrane. Defective trafficking of human AQPs can lead to several disease states, for example nephrogenic diabetes insipidus (AQP2) and Sjogren's syndrome (AQP5). In this chapter, we give an overview of what is known about the regulation of eukaryotic AQPs, focusing particularly on structure-function relationships. We discuss the physiological role of AQP regulation, specific regulatory mechanisms and reoccurring themes in both gating and trafficking. (Less)
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