水孔蛋白1的结构与功能

水通道,又称水孔蛋白（ａｑｕａｐｏｒｉｎ,ＡＱＰ）是动植物细胞膜上转运水的特异孔道。ＡＱＰｓ均属主体内在蛋白（ＭＩＰ）家族的成员。ＡＱＰ１是第一个被鉴定的水通道,又称原型分子水通道。它在体内的分布极广,参与多种生理功能,在膜中以四聚体的形式存在,每一单体形成一个功能性的水通道。ＡＱＰ１的表达可受汞、雌激素等多种因子的调节,并发现它与许多病理生理过程有着直接的关系。     

水通道蛋白的结构与功能研究

水通道蛋白是近年来才被发现的一种转运水分子和某些小分子物质的跨膜蛋白,本文综述了水通道蛋白的分子结构、组织分布及在泌尿、呼吸、消化、神经系统等方面的重要生理学功能。水通道蛋白的研究对阐明某些水代谢疾病的发病机制及为该类疾病提供新的治疗思路具有深远意义。     

水通道蛋白的结构与功能研究

水通道蛋白是近年来才被发现的一种转运水分子和某些小分子物质的跨膜蛋白,本文综述了水通道蛋白的分子结构、组织分布及在泌尿、呼吸、消化、神经系统等方面的重要生理学功能.水通道蛋白的研究对阐明某些水代谢疾病的发病机制及为该类疾病提供新的治疗思路具有深远意义.     

水通道的分子生物学研究

水通道是哺乳动物及植物细胞膜上转运水的特异孔道。第一个水通道蛋白即原型分子水通道（２８ｋＤ通道构成整合膜蛋白）的ｃＤＮＡ序列是在１９９１年完成鉴定的。目前从哺乳动物组织中已鉴定出至少五种水通道蛋白,统称为水蛋白（ａｑｕａｐｏｒｉｎ,ＡＱＰ）,均属于主体内在蛋白（ＭＩＰ）家族的成员。水通道介导水依渗透梯度方向运动。不同的水通道蛋白在组织中的分布不同,但多在肾髓质有表达。原型分子水通道蛋白在膜中以四聚体形式存在,每一单体形成一个功能性的水孔道。     

水孔蛋白在细胞延长、盐胁迫和光合作用中的作用

水孔蛋白属于一个高度保守的、能够进行跨生物膜水分运输的通道蛋白MIP家族。水孔蛋白作为膜水通道,在控制细胞和组织的水含量中扮演重要角色。本研究的重点是属于PIP亚家族的GhPIP1;2和属于TIP亚家族的γTIP1在植物细胞延长中的作用。使用特异基因探针的Northern杂交和实时荧光PCR技术证明GhPIP1;2和GhγTIP1主要在棉花纤维延长过程中显著表达,且最高表达量在开花后5d。在细胞延长过程中,GhPIP1;2和GhγTIP1表达显著,表明它们在促使水流迅速进入液泡这一过程中扮演重要角色。而且也研究了盐胁迫植物中钙离子对水孔蛋白的影响。分别或一起用NaCl或CaCl2处理原生质体或细胞质膜。结果发现在盐胁迫条件下,水渗透率值在原生质体和质膜颗粒中都下降了,同时PIP1水孔蛋白的含量也下降了,表明NaCl对水孔蛋白的功能和含量有抑制作用。同时也观察了Ca2+的两种不同的作用。感知胁迫的胞质中游离钙离子浓度的增加可能导致水孔蛋白的关闭。而过剩的钙离子将导致水孔蛋白的上游调控。同时实验已经证明大麦的一类水孔蛋白-HvPIP2;1有更高的水和CO2转移率。本研究的目标是确定负责转运水和CO2的关键水孔蛋白...     

水通道蛋白的基本结构与特异性通透机理

水通道蛋白是一个具有跨膜运输水分子功能的蛋白家族。从1988年Agre等发现水通道蛋白起,目前在不同物种中已经发现了200余种水通道蛋白,其中存在哺乳动物体内的有13种。概述了水通道蛋白的结构、组织特异性分布及特异性通透机理。     

植物水孔蛋白

水孔蛋白的发现丰富了人们对水分跨膜转运机制的认识,植物水孔蛋白在水分吸收、渗透调节、细胞的伸长和气孔运动等方面都有重要作用。现对植物水孔蛋白的结构特征、多样性、生理学功能、活性调节以及水孔蛋白与环境因子的关系等方面的研究进展进行综述。     

2003年度诺贝尔化学奖和生理医学奖揭晓

瑞典皇家科学院于 1 0月 8日宣布 ,授予美国科学家彼德·阿格雷、罗德里克·麦金农 2 0 0 3年化学奖 ,以表彰他们在细胞膜通道研究中做出的开创性工作。 1 0 0多年前 ,科学家就推测细胞中存在输送水分子的特殊通道 ,但直到 1 988年 ,在阿格雷成功地分离出一种膜蛋白后 ,人们才意识到这就是科学界在漫长岁月中苦苦探索的细胞膜水通道。由此 ,生物体水通道的生理学、生物化学和遗传学研究得以迅速开展。另一种细胞膜通道———细胞膜离子通道能够产生信号 ,在神经系统中传递信息 ,它与神经系统和肌肉方面的许多疾病有关。麦金农于 1 998年对钾…     

水通道

水通道邱俭,陈宜张（第二军医大学生理学教研室,上海２００４３３）关键词水通道,水通道蛋白进出细胞的水转运对细胞稳态是重要的。水通过脂质双层的运动很慢,这是一个单纯扩散过程,活化能高（＞１０ｋｃａｌ／ｍｏｌ）,且对汞化合物不敏感。过去曾认为其他一些细胞...     

水通道蛋白

水通道蛋白 (aquaporin,AQP)是对水专一的通道蛋白 ,普遍存在于动、植物及微生物中。它所介导的自由水快速被动的跨生物膜转运 ,是水进出细胞的主要途径。1　水通道蛋白的发现长期以来 ,普遍认为细胞内外的水分子是以简单的跨膜扩散方式来透过脂双层膜。后来由于在生物物理学研究中发现红细胞及近端肾小管对渗透压改变引起的水的通透性很高 ,很难单纯以弥散来解释。因此 ,一些学者推测水的跨膜转运除了简单扩散外 ,还存在某种特殊的机制 ,并提出了水通道的概念。1988年 ,Agre等在鉴定人类 Rh血型抗原时 ,偶然在红细胞膜上发现了 1种新的 2…     

Current knowledge on aquaporin water channels: clinical implications

The discovery of the aquaporin family of water channels has explained to a high degree the mechanism of water transport across cell membranes. The molecular structure of the first purified aquaporin shows its tetrameric organization with each subunit containing an individual aqueous pore selectively permeable for water but not for protons. At least 11 human aquaporins have been identified. Definition of sites of their expression enabled explanation of their physiological role as well as pathological importance in congenital cataract or nephrogenic diabetes insipidus.     

Aquaporins in health and disease

The molecular basis of membrane water-permeability remained elusive until the recent discovery of the aquaporin water-channel proteins. The fundamental importance of these proteins is suggested by their conservation from bacteria through plants to mammals. Ten mammalian aquaporins have thus far been identified, each with a distinct distribution. In the kidney, lung, eye and brain, multiple water-channel homologs are expressed, providing a network for water transport in those locations. It is increasingly clear that alterations in aquaporin expression or function can be rate-limiting for water transport across certain membranes. Aquaporins are likely to prove central to the pathophysiology of a variety of clinical conditions from diabetes insipidus to various forms of edema and, ultimately, they could be a target for therapy in diseases of altered water homeostasis.     

Aquaporin water channels: molecular mechanisms for human diseases

Although water is the major component of all biological fluids, the molecular pathways for water transport across cell membranes eluded identification until the discovery of the aquaporin family of water channels. The atomic structure of mammalian AQP1 illustrates how this family of proteins is freely permeated by water but not protons (hydronium ions, H3O+). Definition of the subcellular sites of expression predicted their physiological functions and potential clinical disorders. Analysis of several human disease states has confirmed that aquaporins are involved in multiple different illnesses including abnormalities of kidney function, loss of vision, onset of brain edema, starvation, and arsenic toxicity.     

Plant aquaporins: novel functions and regulation properties

Aquaporins are water channel proteins of intracellular and plasma membranes that play a crucial role in plant water relations. The present review focuses on the most recent findings concerning the molecular and cellular properties of plant aquaporins. The mechanisms of transport selectivity and gating (i.e. pore opening and closing) have recently been described, based on aquaporin structures at atomic resolution. Novel dynamic aspects of aquaporin subcellular localisation have been uncovered. Also, some aquaporin isoforms can transport, besides water, physiologically important molecules such as CO(2), H(2)O(2), boron or silicon. Thus, aquaporins are involved in many great functions of plants, including nutrient acquisition, carbon fixation, cell signalling and stress responses.     

Birth of water channel proteins-the aquaporins

If we compare aquaporin (as a proteic pathway for water permeation across biological membranes) with a child we can say that he had a very long gestation period. His possible existence was predicted for a long time (Overton in 1985, Stein and Danielli in 1956), some of his features (transport of water and its reversible inhibition) were assigned by Macey and Farmer in 1970, however this child was first detected by Benga and coworkers in 1986. We clearly demonstrated for the first time the presence and location of a water channel at the human RBC membrane among the polypeptides migrating in the region having 35-60 kDa on the electrophoretogram of RBC membranes, labeled with 203Hg-PCMBS in the conditions of specific inhibition of water diffusion; I suggested that a minor membrane protein that binds PCMBS is involved in water transport and also indicated the way in which the specific protein could be further characterized: by purification and reconstitution in liposomes. Our landmark papers in 1986 can be compared with the first detection of a child "in utero" by ultrasonography, since we discovered one of the essential components of the "aquaporin child" (a molecular weight of 35-60 kDa for the glycosylated component); we have also indicated the way to recognize him after birth (among other children of his group!): placing the isolated children in a certain environment and asking them to perform the same task (one should read: reconstitution studies in liposomes and measurement of water permeability), like aligning athletes for a running test. This was the only certain way to know that the child is really the fastest runner and not just one that is helping (by various means) another child to be fastest runner. A "new child" was observed in 1988 by Agre and coworkers, who identified a novel integral membrane protein in human RBCs having a non-glycosylated component of 28 kDa and a glycosylated component migrating as a diffuse band of 35-60 kDa; they suggested that the new protein (nick-named CHIP28 in 1991) may play a role in linkage of the membrane skeleton to the lipid bilayer. In 1992 Agre and coworkers suggested that CHIP28 is a functional unit of membrane water channels; by reconstitution in liposomes it was demonstrated that CHIP28 is a water channel itself rather than a water channel regulator. In other words the child we first detected was recognized as having the predicted qualities only in 1992. In 1993 CHIP28 was renamed aquaporin 1. Looking in retrospect, asking the crucial question, when was the first water channel protein, aquaporin 1, discovered, a fair and clear cut answer would be: the first water channel protein, now called aquaporin 1, was identified or "seen" in situ in the human RBC membrane by Benga and coworkers in 1986. It was again "seen" when it was by chance purified by Agre and coworkers in 1988 and was again identified when its main feature, the water transport property was found by Agre and coworkers in 1992. If a comparison with the discovery of The New World of America is made, the first man who has "seen" a part, very small indeed, of The New Land was Columbus; later, others, including Amerigo Vespucci (from whom the name derived), have better "seen" a larger part of the new Continent and in the subsequent years many explorers discovered the complexity of the Americas!     

The role of aquaporins in root water uptake

The capacity of roots to take up water is determined in part by the resistance of living tissues to radial water flow. Both the apoplastic and cell-to-cell paths mediate water transport in these tissues but the contribution of cell membranes to the latter path has long been difficult to estimate. Aquaporins are water channel proteins that are expressed in various membrane compartments of plant cells, including the plasma and vacuolar membranes. Plant aquaporins are encoded by a large multigene family, with 35 members in Arabidopsis thaliana, and many of these aquaporins show a cell-specific expression pattern in the root. Mercury acts as an efficient blocker of most aquaporins and has been used to demonstrate the significant contribution of water channels to overall root water transport. Aquaporin-rich membranes may be needed to facilitate intense water flow across root tissues and may represent critical points where an efficient and spatially restricted control of water uptake can be exerted. Roots, in particular, show a remarkable capacity to alter their water permeability over the short term (i.e. in a few hours to less than 2-3 d) in response to many stimuli, such as day/night cycles, nutrient deficiency or stress. Recent data suggest that these rapid changes can be mostly accounted for by changes in cell membrane permeability and are mediated by aquaporins. Although the processes that allow perception of environmental changes by root cells and subsequent aquaporin regulation are nearly unknown, the study of root aquaporins provides an interesting model to understand the regulation of water transport in plants and sheds light on the basic mechanisms of water uptake by roots.     

Plant aquaporins: multifunctional water and solute channels with expanding roles

There is strong evidence that aquaporins are central components in plant water relations. Plant species possess more aquaporin genes than species from other kingdoms. According to sequence similarities, four major groups have been identified, which can be further divided into subgroups that may correspond to localization and transport selectivity. They may be involved in compatible solute distribution, gas-transfer (CO2, NH3) as well as in micronutrient uptake (boric acid). Recent advances in determining the structure of some aquaporins gives further details on the mechanism of selectivity. Gating behaviour of aquaporins is poorly understood but evidence is mounting that phosphorylation, pH, pCa and osmotic gradients can affect water channel activity. Aquaporins are enriched in zones of fast cell division and expansion, or in areas where water flow or solute flux density would be expected to be high. This includes biotrophic interfaces between plants and parasites, between plants and symbiotic bacteria or fungi, and between germinating pollen and stigma. On a cellular level aquaporin clusters have been identified in some membranes. There is also a possibility that aquaporins in the endoplasmic reticulum may function in symplasmic transport if water can flow from cell to cell via the desmotubules in plasmodesmata. Functional characterization of aquaporins in the native membrane has raised doubt about the conclusiveness of expression patterns alone and need to be conducted in parallel. The challenge will be to elucidate gating on a molecular level and cellular level and to tie those findings into plant water relations on a macroscopic scale where various flow pathways need to be considered.     

The aquaporins

Water is the major component of all living cells, and efficient regulation of water homeostasis is essential for many biological processes. The mechanism by which water passes through biological membranes was a matter of debate until the discovery of the aquaporin water channels. Aquaporins are intrinsic membrane proteins characterized by six transmembrane helices that selectively allow water or other small uncharged molecules to pass along the osmotic gradient. In addition, recent observations show that some aquaporins also facilitate the transport of volatile substances, such as carbon dioxide (CO₂) and ammonia (NH₃), across membranes. Aquaporins usually form tetramers, with each monomer defining a single pore. Aquaporin-related proteins are found in all organisms, from archaea to mammals. In both uni- and multicellular organisms, numerous isoforms have been identified that are differentially expressed and modified by post-translational processes, thus allowing fine-tuned tissue-specific osmoregulation. In mammals, aquaporins are involved in multiple physiological processes, including kidney and salivary gland function. They are associated with several clinical disorders, such as kidney dysfunction, loss of vision and brain edema.