Structure and function of aquaporin water channels

Abstract

The aquaporins (AQPs) are a family of small membrane-spanning proteins (monomer size approximately 30 kDa) that are expressed at plasma membranes in many cells types involved in fluid transport. This review is focused on the molecular structure and function of mammalian aquaporins. Basic features of aquaporin structure have been defined using mutagenesis, epitope tagging, and spectroscopic and freeze-fracture electron microscopy methods. Aquaporins appear to assemble in membranes as homotetramers in which each monomer, consisting of six membrane-spanning alpha-helical domains with cytoplasmically oriented amino and carboxy termini, contains a distinct water pore. Medium-resolution structural analysis by electron cryocrystallography indicated that the six tilted helical segments form a barrel surrounding a central pore-like region that contains additional protein density. Several of the mammalian aquaporins (e.g., AQP1, AQP2, AQP4, and AQP5) appear to be highly selective for the passage of water, whereas others (recently termed aquaglyceroporins) also transport glycerol (e.g., AQP3 and AQP8) and even larger solutes (AQP9). Evidence for possible movement of ions and carbon dioxide through the aquaporins is reviewed here, as well as evidence for direct regulation of aquaporin function by posttranslational modification such as phosphorylation. Important unresolved issues include definition of the molecular pathway through which water and solutes move, the nature of monomer-monomer interactions, and the physiological significance of aquaporin-mediated solute movement. Recent results from knockout mice implicating multiple physiological roles of aquaporins suggest that the aquaporins may be suitable targets for drug discovery by structure-based and/or high-throughput screening strategies.

Aquaporin structure–function relationships: Water flow through plant living cells

“…There are various isoforms of plant TIP: alpha (seed), gamma, root (Rt), and water-stress induced (Wsi). These proteins may allow the diffusion of water, amino acids and/or peptides from the tonoplast interior to the cytoplasm [21][22][23][24][25][26]. The plasma membrane aquaporins (PIPs) can be divided into two subfamilies: PIP1 with inactive or low waterchannel activity and PIP2 with high water-channel activity [27].…”

“…Discovery of the aquaporin family of water channel proteins has provided a molecular explanation for rapid water movements across the plasma membranes of cells while diffusion still works in parallel [9,26,28]. This may be one reason for the abundance and diversity of aquaporins, in particular in plants.…”

“…Regardless of whether all or only the majority of the plant MIPs are aquaporins, it is clear that a large number of aquaporins are present in plants, some localized in the tonoplast, some in the plasma membrane and some possibly localized in endomembranes [4,6,11,18,20,21,26,32,45]. MIP-B was found in fractions containing tonoplast proteins and possibly in a fraction of intermediate density, distinct from both plasma membrane and tonoplast, and also distinct from the fractions in which MIP-A was located [19,34,50].…”

“…Multiple aquaporin genes could allow for variable expression in different tissues, cells and intracellular membranes during development, under changing external conditions and in response to rapidly changing demands for water movement [4,6,11,18,20,21,26,32,45,50,52]. Höfte et al found that a presumptive tonoplast aquaporin (Phaseollus ␣-TIP) is located in multivesicular bodies in transgenic tobacco that expresses Phaseollus ␣-TIP [53].…”

“…2). The six transmembrane domains were predicted to be ␣-helices, packed together with the pore-forming domains outside and towards the center of an aquaporin tetramer [4,26,28,56]. There are five loops (A-E) joining the transmembrane helices.…”