The Aquaporins, Blueprints for Cellular Plumbing Systems

Abstract

Membrane Water PermeabilityPlasma membranes provide an effective barrier to the extracellular environment. Water was long believed to move through lipid bilayers by simple diffusion; however, membranes from different tissues vary in their permeability to water. The variability is particularly evident in mammalian kidney where proximal tubules and descending thin limbs of Henle's loop have constitutively high water permeability and are responsible for reabsorption of more than 150 liters per day in adult humans. In contrast, ascending thin limbs have very low water permeability. Renal distal tubules empty into collecting ducts where stimulation with vasopressin causes an increase in water permeability (see Ref. 1 for review). These observations led to the suggestion that specialized water transport molecules must exist in membranes with intrinsically high water permeability. Nevertheless, despite extensive studies, the molecular identity of water transport proteins remained elusive until recently.The well defined features of membrane water permeability permitted serendipitous identification of the first known water channel. While purifying the 32-kDa subunit of the red cell Rh blood group antigen, a new 28-kDa polypeptide was discovered (2). Detailed biochemical studies of this newly identified tetrameric membrane protein were made easy by its low solubility in N-lauroylsarcosine, which permitted simple purification (3). The abundance of the protein in rat renal proximal tubules and descending thin limbs (2) sparked the idea that the 28-kDa polypeptide may be the long sought water channel, and its unique N-terminal amino acid sequence permitted cloning from an erythroid cDNA library (4). Functional Analyses of AQP1The Xenopus oocyte expression system has been extremely useful for study of water transport. Oocytes injected with cRNA for the 28-kDa polypeptide exhibit remarkably high osmotic water permeability (P f ϳ200 ϫ 10 Ϫ4 cm s Ϫ1) and rapidly explode in hypotonic buffer (Fig. 1), whereas control oocytes exhibit minimal permeability (5). First referred to as "CHIP28," this protein is now designated aquaporin-1 (AQP1) 1 by the Human Genome Nomenclature Committee (see http://www.gene.ucl.ac.uk/nomenclature). Despite its large water permeability, AQP1 failed to confer a measurable increase in membrane currents (5). Consistent with these results, highly purified AQP1 protein reconstituted into proteoliposomes exhibits high unit water permeability (P f ϳ3 ϫ 10 9 water molecules subunit Ϫ1 s Ϫ1 ), whereas permeation by other small solutes or even protons was undetectable (6). The prevailing view is that AQP1 is a constitutively active, water-selective pore that permits osmotically driven movement of water. A report that forskolin induces a cation current in AQP1-expressing oocytes (7) was not reproduced by multiple other scientific groups. Permeation by CO 2 has recently been proposed, because rates of pH change are about 40% higher in oocytes expressing AQP1 (8). Permeation by O 2 , nitric oxide, and other gases is...

Members of the aquaporin family in the developing pea seed coat include representatives of the PIP, TIP, and NIP subfamilies

“…It may be anticipated that aquaporins are involved in the efflux of water from the parenchyma cells. Aquaporins belong to the family of major intrinsic proteins (MIPs), an ancient family with members in all life forms (Agre et al, 1998;. Based on sequence homology, members of the MIP family in higher plants fall into four major subgroups: plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), Nodulin 26-like MIPs (NLMs or NIPs), and small, basic intrinsic proteins (SIPs).…”

“…Functionally, MIPs fall into two main categories: aquaporins and glycerol facilitators (Heymann and Engel, 1999;Agre et al, 1998). High-resolution atomic structures of prototypes of each category, aquaporin-1 (AQP1) from mammals and the glycerol facilitator (GlpF) from Escherichia coli, have elucidated aspects of the selectivity of these transporters (Fu et al, 2000;Sui et al, 2001).…”

Involvement of aquaporins in colorectal carcinogenesis

“…Thus far, 10 mammalian AQPs have been identified, each with a distinct tissue distribution (King and Agre, 1996). In the kidney, lung, eye, and brain, multiple water-channel homologues are expressed, providing a network for water transport in those locations, and it was assumed that alterations in AQP expression or function can be rate-limiting for water transport across certain membranes (King and Agre, 1996;King et al, 1997;Agre et al, 1998). Therefore, it was believed that AQPs have some valuable role in human pathophysiology and that changes in such specific pathways have the potential to cause disease or to be the basis of treatment (King et al, 2000).…”

Cerebral Cortical Aquaporin‐4 Expression in Brain Edema following Cardiac Arrest in Rats

“…AQPs are freely permeable to water but not to ions or to charged solutes. 19 Ten AQPs have been identified, each with a distinct distribution in the kidneys, lung, eye, and brain. AQP4 is the most abundant AQP throughout the central nervous system and covers more than 95% of the surface of brain capillaries, suggesting it could play an important role in the regulation of extravascular brain water in the central nervous system.…”