Aquaporin
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Aquaporins are a class of integral membrane proteins that form pores in the membrane of biological cells and selectively conduct water molecules in and out, while preventing the passage of ions and other solutes. Also known as water channels, they are each composed of four (typically) identical subunit proteins. Water molecules traverse the narrowest portion of the channel single file. The presence of water channels increases the permitivity of membranes to water by as much as ten fold. However, because the process is passive, aquaporin cannot reverse the direction of the osmotic gradient driving the flow of water. Many human cell types express them, as do certain bacteria and many other organisms, such as plants for which it is essential for the water transport system. There are two highly conserved sequence motifs asparagine-proline-alanine (..NPA..) (see reference 1.). Genetic defects involving aquaporin genes have been associated with several human diseases. The 2003 Nobel Prize in Chemistry was awarded to Peter Agre (jointly with Roderick MacKinnon for his work on potassium channels) for his discovery of aquaporins and elucidation of their structures and functions.
There are ten known types of aquaporins, and six of these are located in the kidney. The most studied aquaporins are AQP1, AQP2, AQP3, and AQP4.
Aquaporin 1
AQP1 is a widely expressed water channel, whose physiological function has been most thoroughly characterized in the kidney. It is found in the basolateral and apical plasma membranes of the proximal tubules, the descending limb of the loop of Henle, and in the descending portion of the vasa recta. Additionally, it is found in red blood cells, vascular endothelium, the gastrointestinal tract, sweat glands, and lungs. It is not regulated by vasopressin (ADH).
Aquaporin 2
AQP2 is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. This aquaporin is regulated in two ways by the peptide hormone vasopressin: short-term regulation (minutes) through trafficking of AQP2 vesicles to the apical region where they fuse with the apical plasma membrane, and long-term regulation (days) through an increase in AQP2 gene expression. Mutations in this channel are associated with nephrogenic diabetes insipidus, which can be either autosomal dominant or recessive. Lithium, which is often used to treat bipolar disorder, can cause acquired diabetes insipidus by decreasing the expression of the AQP2 gene. This can result in debilitating increases in the rate of urine production. The expression of the AQP2 gene is increased during conditions associated with water retention such as pregnancy and congestive heart failure.
Aquaporins 3 and 4
These aquaporins are found in the basolateral cell membrane of principal collecting duct cells and provide a pathway for water to exit these cells. In kidney, AQP3 gene expression is regulated by vasopressin (ADH), whereas AQP4 is constitutively expressed. AQP4 is expressed in astrocytes and are upregulated by direct insult to the central nervous system.
External links
Aquaporins (AQPs) ”water pore” are membrane proteins that function as water-specific channels.
History
In most cells, water moves in and out by diffusion through the lipid component of cell membranes. Due to the relatively high water permeability of some epithelial cells it was long suspected that some additional mechanism for water transport across membranes must exist, but it was not until 1992 that the functional characterization of the first aquaporin, ‘aquaporin-1’, was reported by Peter Agre, then of Johns Hopkins University and now a professor and administrator at Duke University. The pioneering discoveries and research on water channels by Agre and his colleagues resulted in the presentation of a Nobel Prize in Chemistry to Agre in 2003. In 2000, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of an aquaporin, viz. aquaporin-1. Further studies using supercomputer simulations have identified the pathway of water as it moves through the channel and demonstrated how a pore can allow water to pass without the passage of small solutes.
Structure
Aquaporins form tetramers in the cell membrane, and facilitate the transport of water and, in some cases, other small solutes, such as glycerol, across the membrane. However, the water pores are completely impermeable to charged species, such as protons, a property critical for the conservation of membrane's electrochemical potential. The aquaporins are predicted to have six membrane-spanning segments, existing in the plasma membrane as homotetramers. Each aquaporin monomer contains two hemi-pores, which fold together to form a water channel
Using computer simulations it has been suggested that the orientation of the water molecules moving through the channel assures that only water passes between cells, due to the formation of a single line of water molecules. The water molecules move through the narrow channel by orienting themselves in the local electrical field formed by the atoms of the channel wall. Upon entering, the water molecules face with their oxygen atom down the channel. Midstream, they reverse orientation, facing with the oxygen atom up. While passing through the channel, the single-file chain of water molecules streams through, always entering face down and leaving face up. The strictly opposite orientations of the water molecules keep them from conducting protons (or rather oxonium ions, H3O+), while still permitting a fast flux of water molecules .
Aquaporins in mammals
Water crosses the cell membrane by either diffusing through the phospholipid bilayer or by passing through special water channels called aquaporins. More than 10 mammalian aquaporins have so far been identified, but the existence of many more is suspected. Most aquaporins appear to be exclusive water channels that will not allow permeation of ions or other small molecules. Some aquaporins - known as aquaglyceroporins - transport water plus glycerol and a few other small molecules.
Aquaporins play a key role in control of water excretion by the kidney. Vasopressin (also known as "antidiuretic hormone") is a circulating peptide that regulates aquaporin-2 to result in variable and tightly regulated water excretion. When vasopressin levels rise in the blood, the collecting duct cells in the kidneys bind more vasopressin, initiating a complex signaling process, which results in movement of aquaporin-2-containing intracellular vesicles to the plasma membrane. These vesicles fuse with the plasma membrane, thus increasing the water permeability of the cells and allowing increased return of water from the nascent urine to the blood. When vasopressin levels in the blood fall, the aquaporin-2 is retrieved by endocytosis into intracellular storage sites. The removal of aquaporin-2 from the plasma membrane lowers the water permeability of the collecting duct cells, causing more water to be retained in the excreted urine.
Aquaporins in plants
In plants water is taken up from the soil through the roots, where it passes from the cortex into the vascular tissues. There are two routes for water to flow in these tissues, known as the; apoplastic and symplastic pathways. The presence of aquaporins in the cell membranes seems to serve to facilitate the transcellular symplastic pathway for water transport. When plant roots are exposed to mercuric chloride, which is known to inhibit aquaporins, the flow of water is greatly reduced while the flow of ions is not, supporting the view that there exists a mechanism for water transport independent of the transport of ions; aquaporins.
Aquaporins and Disease
There have been two clear examples of diseases identified as resulting from mutations in aquaporins:
- Mutations in the aquaporin-2 gene cause hereditary nephrogenic diabetes insipidus in humans.
- Mice homozygous for inactivating mutations in the aquaporin-0 gene develop congenital cataracts.
In addition to its role in genetically determined nephrogenic diabetes insipidus, aquaporins also play a key role in acquired forms of nephrogenic diabetes insipidus (disorders that cause increased urine production). Acquired nephrogenic diabetes insipidus can result from impaired regulation of aquaporin-2 due to administration of lithium salts (as a treatment for bipolar disorder), low potassium concentrations in the blood (hypokalemia), high calcium concentrations in the blood (hypercalcemia), or a chronically high intake of water beyond the normal requirements (e.g. due to excessive habitual intake of bottled water or coffee).
References
- 1-[link]
- [Open Source Review Article on Aquaporins]
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