Aquaporins: Structure, Systematics, and Regulatory Features A
Total Page：16
File Type：pdf, Size：1020Kb
Russian Journal of Plant Physiology, Vol. 51, No. 1, 2004, pp. 127–137. Translated from Fiziologiya Rastenii, Vol. 51, No. 1, 2004, pp. 142–152. Original Russian Text Copyright © 2004 by Shapiguzov. REVIEWS Aquaporins: Structure, Systematics, and Regulatory Features A. Yu. Shapiguzov Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Botanicheskaya ul. 35, Moscow, 127276 Russia; fax: 7 (095) 977-9372; e-mail: [email protected] Received May 13, 2003 Abstract—The review describes current views on the molecular structure, systematics, and functional regula- tion of aquaporins. These recently discovered channel proteins play a principal role in water transport across cell membranes in the majority of living organisms. Key words: aquaporins - cell membranes - water relations INTRODUCTION family—is sometimes used for aquaporins in the litera- ture. Multicellular organisms have developed specialized Presently, the number of discovered aquaporins tissues with low hindrance to water flows. Nonetheless, exceeds two hundred, and the plant aquaporins consti- the transfer of water molecules across the cell mem- tute a considerable part of this family [10]. For exam- brane is the main step in water transport [1]. ple, Arabidopsis thaliana genome contains 35 aqua- The ability of cells to control outward or inward porin genes [11–13], and Zea mays contains more than movement of water and solutes is a matter of principal 30 such genes [14]. significance. Cell membranes represent selective com- Water transport is extremely difficult for quantita- plex filters that regulate the transport of ions, organic tive assessment. Unlike the transmembrane ion trans- substances, and water. The current knowledge of mem- port associated with membrane potential changes, brane structure and functions is rapidly expanding [2]. water transport is normally evaluated from the osmoti- A number of transmembrane carrier proteins have been cally induced changes of the cell volume, and such discovered and characterized. However, despite this measurements are often complicated [15]. Further- progress, molecular basis of the transmembrane water more, a background component of water transport is transport remained poorly understood until recently. rather high owing to universal abundance of water and The water permeability of biological membranes was its rapid diffusion through the lipid bilayer. commonly attributed to diffusion of water across the The oocytes of a frog Xenopus played an important lipid bilayer. However, some physiological processes role in studying water carriers [16]. The membranes of are associated with translocation of large amounts of these cells feature a very low intrinsic permeability to water or with rapid changes in membrane permeability water. When mRNA is injected into the oocyte, it is nor- to water. Such phenomena cannot be explained by mally expressed as a functional protein. After the injec- water diffusion across the lipids, which implicates the tion of aqp1 gene mRNA, the water permeability of the existence of water-carrying proteins. oocyte membrane increased manyfold; the cell swelled The first of such carriers was revealed in the mam- rapidly in a hypoosmotic buffer and lysed. By compar- malian erythrocytes whose cell membrane is highly ing the kinetics of cell volume changes in untreated and permeable to water [3]. The initial observation that aqp1-expressing oocytes, it was possible to assess the activity of the protein examined. HgCl2 and organic–mercurial substances inhibit water transport implied the involvement of protein in this pro- Another important approach to studying aquaporins cess [4]. A specific polypeptide was isolated later and is the evaluation of their activity in proteoliposomes termed CHIP28 (channel-like integral protein of 28 kD) [17]. [5, 6]. Several homological proteins were revealed in The investigation of aquaporins led to several other mammalian tissues. One of such proteins, called important conclusions. (1) Many aquaporins signifi- MIP (major intrinsic protein of lens), had been known cantly reduce the activation energy for the transmem- for a long time although its function was unclear [7]. brane water transfer. The rate of water movement Later studies demonstrated the presence and, in some across the channel approaches to the diffusion rate in cases, abundance of homological proteins in many bulk water [17, 18]. (2) Aquaporins provide for bidirec- organisms [8], and their transport activity was proven. tional passage of water, and the transport direction is A term “aquaporins” (Aqp) was adopted, and CHIP28 determined by physical conditions of the medium [19, was renamed as Aqp1 [9]. An alternative term—MIP 20]. (3) Water transport is passive: it does not require 1021-4437/04/5101-0127 © 2004 MAIK “Nauka /Interperiodica” 128 SHAPIGUZOV energy supply, and water moves downhill the gradient proteins is an inherent homology between the halves of of water potential [20]. (4) Aquaporin channels are their molecules. The repeated sequences are oriented in highly selective. The water transport across the cell the same direction. It is likely that the aquaporin gene membrane normally occurs without a concomitant originated from the duplication of a half-sized gene [10]. transfer of any ion species, including protons [21, 22]. Six transmembrane α-helical protein domains form (5) Many aquaporins are sensitive to mercury-contain- a barrel-like configuration in the membrane plane. The ing inhibitors. The mercury atoms bind to conserved amino- and carboxy-terminal domains face the cyto- cysteine residues and are thought to block water pas- plasm and account for a specific regulation of aqua- sage through the channel by steric hindrance [23, 24]. porin activity. One of the cytoplasmic loops and one of There is evidence that mercury induces conformational the periplasmic loops comprise two short α-helical changes in aquaporins [25]. domains on the opposite sides of the “barrel.” These Some aquaporins turned out to be specific not so domains participate in the formation of the water chan- much to water as to glycerol and several other sub- nel. The tops of these domains are located in close stances [26], for example, gases [20, 27]. Some aqua- proximity to each other inside the molecule (Fig. 1). porins, including aquaporins of plant origin, are perme- Each of these tops contains an NPA (Asn-Pro-Ala) able to formamide [28] and urea [29]. The substrate motif, which is conserved for all aquaporins with rare specificity of these proteins in plants is still unknown. exceptions [14, 46]. This type of structure was called There is evidence that aquaporins are permeable to eth- the “hourglass model” [19, 47]. anol and methanol; however, the study of this phenome- When incorporated into the membrane, aquaporins non is highly complicated owing to unhampered diffu- produce homotetramers [48, 49]. Apparently, this sion of alcohols through the lipid bilayer [30]. The aqua- assemblage is required for correct folding and stability porins of Chara corallina are permeable to H2O2 [31]. of the protein, as well as for protein sorting and post- The expression of Aqp1 increases the CO2 perme- translational modifications including glycosylation. ability of the Xenopus oocyte membrane [32], although Each of the four subunits within the complex produces the significance of this property for the mammalian an independent water channel, whereas the pore for the physiology in vivo was questioned in some works [33, aforementioned cGMP-dependent ion transport is ori- 34]. Mercury-containing organic substances inhibit ented along to the tetramer axis (Fig. 2) [39]. The sta- CO2 transport across the plasma membrane in cyano- bility of the quaternary structure varies for different bacteria Synechococcus [35] and in higher plants [36]. phylogenetic clusters of aquaporins: the tetramers of This provides evidence for CO2-transporting activity of aquaporins with glycerol specificity are less stable [50]. aquaporins and suggests their involvement in photosyn- The most complete data about the structure of water thesis; nevertheless, this topic remains poorly understood. channel were obtained after crystallization of Aqp1 It is possible that some aquaporins are permeable to other [51] and its X-ray crystallographic analysis [52, 53]. gases, including O2, NH3, and NO [27]. The attempts to Most likely the structural features discovered for Aqp1 study this issue encounter the problem of high permeabil- are also valid for other water-conducting proteins of the ity of lipids to the substances mentioned [37]. family. A small part of Aqp1 molecules expressed in Xenopus The shape of the aquaporin channel is reminiscent oocytes becomes permeable to Na+ after the intracellular of a dumb-bell (Fig. 3). The channel consists of an injection of cyclic GMP [38]. Apparently, the binding of external and cytoplasmic funnels and a long selective cGMP results in the opening of the cationic channel in pore with connecting them. The funnel surface consists the aquaporin molecule. The formation of aqueous and mainly of polar amino-acid residues. Here the hydro- cationic pores seems to occur in different regions of the philic substrates undergo primary selection and their protein molecule (see below) [39]. The ionic perme- hydration shell is removed at the expense of hydrogen ability was also demonstrated for Aqp0 [40–42], Aqp6 bond formation with the protein atoms. The funnels of [43, 44], and plant aquaporin Nod26 [45]. Further glycerol-specific aquaporins are less