Cellular Distribution of the Aquaporins: A Family of Water Channel Proteins

Line
Title: Cellular Distribution of the Aquaporins: A Family of Water Channel Proteins
Authors: Brown, Dennis; Katsura, Toshiya; Kawashima, Megumi; Verkman, Alan S.; Sabolic, Ivan
Publisher: Histochemistry & Cell Biology
Date Published: July 01, 1995
Reference Number: 209
Line
Abstract • Translation
A group of transmembrane proteins that are related to the major intrinsic protein of lens fibers (MIP26) have been named "aquaporins" to reflect their role as water channels. These proteins are located at strategic membrane sites in a variety of epithelia, most of which have well-defined physiological functions in fluid absorption or secretion. However, some aquaporins have been localized in cell types where their role is at present unknown. Most of the aquaporins are delivered to the plasma membrane in a non-regulated (constitutive) fashion, but AQP2 enters the regulated exocytotic pathway and its membrane expression is controlled by the action of the antidiuretic hormone, vasopressin. These pathways of constitutive versus regulated delivery to the plasma membrane have been reconstituted in transfected LLC-PK1 epithelial cells, indicating that the information encoded within the protein sequence is sufficient to allow sorting of newly synthesized protein into distinct intracellular vesicles. Finally, different members of the aquaporin family can be targeted to apical, basolateral or both apical and basolateral plasma membrane domains of polarized epithelial cells. This implies that signals for the polarized targeting of these proteins also is located in non-homologous regions of these similar proteins. Thus, future investigations on the aquaporin family of proteins will provide important information not only on the physiology of membrane transport processes in many cell types, but also on the targeting and trafficking signals that allow proteins to enter distinct intracellular vesicular pathways in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Cells are encircled by a thin layer of tissue called a cell or plasma membrane. The cell membrane is comprised of fats (called lipids), proteins and some carbohydrates. To orient yourself to the cell structure, think of it as more of a square than a circle. The sides and bottom of the cell membrane are referred to as the basolateral membrane. The section of the membrane that comprises the top of the cell is referred to as the apical membrane.

Cell membranes are permeable so body water can diffuse through them. In this way, the body is able to maintain body water balance. The degree of permeability varies among different cell types, and sometimes even among different sides of a single cell. For instance, the apical membrane of the principal cells of the kidney collecting duct is relatively impermeable to water while the basolateral membrane is quite water permeable.

Researchers discovered some cells that allowed more water through them than could be accounted for by osmotic diffusion, and they postulated the existence of water channels. Water channels were conceived as molecular structures which, once inserted in the cell membrane, acted as channels through which body water could flow. Because of this, water channels enhance the water permeability of the cell membranes. To date, there are six known AQPs.

AQP1 is located on the membranes of cells that have a high intrinsic water permeability such as the proximal tubule of the kidneys and the descending limb of Henle, also in the kidney. AQP1 is also found in red blood cells, the cell lining of the male reproductive tract, and in the choroid plexus. AQP1 is usually, but not always, located on both the basolateral and apical membranes of the cell.

AQP2 is located in the apical membranes of the principal cells of the kidney collecting duct. AQP3 is found in the basolateral membranes of these same cells. Unlike AQP1 and AQP2, AQP3 allows other molecules than water, such as urea and glycerol, to pass through it. Another AQP is called the mercurial insensitive water channel (MIWC) because, unlike the rest of the AQPs, mercurial compounds cannot prevent it from performing its function. MIWC is found in the basolateral plasma of kidney collecting duct principal cells. It is also located in gastric parietal cell basolateral membranes, in brain and central nervous system cells called astrocytes.

AQP4 is located in the brain. AQP5 is located in the salivary glands and the cornea. AQPs are also found in amphibians and plants. And it is suspected that many AQPs remain to be discovered in all other animal and plant species.

Most of the AQPs are delivered to their respective cell membranes in constant, fixed amounts, regardless of environmental conditions or demand. However, the delivery of AQP2 to the apical membrane of the collecting duct principal cells is regulated by the antidiuretic hormone, vasopressin (VP). According to the shuttle hypothesis, AQP2 waits in little sacs called vesicles within the cell just beneath the apical membrane. When signaled by the presence of VP, these AQP2-bearing vesicles shuttle from their holding sites within the cell to the apical membrane. They fuse with it and the AQP2s insert themselves in the membrane, making it more water permeable. When VP absents itself from the cell, AQP2 is retrieved by the vesicles, which return to their holding sites where they wait till signaled to cycle back to the apical membrane.

This model of AQP2 regulation by VP may need further refinement. The recent availability of cDNAs for AQP2 and AQP1 has allowed researchers to express both water channels in laboratory cell cultures. Brown, et al., recently developed two lines of cells that can retain both AQP1 and AQP2. This enables them to confirm the different modes of AQP regulation.

AQP1 is delivered to the cell membrane in a constitutive (i.e. non-regulated) manner. AQP2's delivery to the cell membrane is regulated by VP. Brown, et al's., laboratory cell culture always shows AQP1 in the cell membrane, whereas AQP2 is found in the membrane only after the cell culture is infused with VP. Further, cells with AQP1 were found to have a high degree of water permeability whereas the cells with AQP2 could only match that level of permeability when infused with VP. Other experiments with these cell cultures indicated that the information required for the recycling process that returns AQP2s from the membrane to its holding site within the cell is encoded in AQP2 itself.