Structure and Function of Kidney Water Channels

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Title: Structure and Function of Kidney Water Channels
Authors: Frigeri, Antonio; Verkman, Alan S.; Shi, Lan-Bo; Hasegawa, Hajime; Skach, M.D., William R.; Van Hoek, Alfred N.; Brown, Dennis; Ma, Tonghui; Mitra, Alok; Farinas, Javier
Publisher: Kidney International
Date Published: October 01, 1995
Reference Number: 207
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Abstract • Translation
There is now firm evidence that water transporting proteins are expressed in renal and extrarenal tissues. In the kidney, proximal-type (CHIP28) and collecting duct (WCH-CD) water channels have been identified. We have cloned three kidney cDNAs with homology to the water channel (aquaporin) family, including a mercurial-insensitive water channel (MIWC), and a glycerol-transporting protein (GLIP) in collecting duct basolateral membrane. To elucidate water transporting mechanisms, a series of molecular and spectroscopic studies were carried out on purified CHIP28 protein and expressed chimeric and mutated CHIP28 cDNAs. The results indicate that CHIP28 transports water selectively, that CHIP28 monomers are assembled in membranes as tetramers, but that individual monomers function independently. Monomers contain multiple membrane-spanning helical domains. Based on these data and recent electron crystallography results, a model for water transport is proposed in which water moves through narrow pores located within individual CHIP28 monomers.

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)

Researchers proposed the existence of water channels over 100 years ago. Water channels were conceived to be molecular units that entered cell membranes to allow water to pass through the membranes in greater quantities than the membrane by itself could allow. In 1992, Preston, et al., proved that the protein called CHIP28 functioned as a water channel. This accelerated the understanding of the structure, function and physiology of water channels. And there is now strong evidence that a family of proteins that act as water channels facilitate water movement in tissues both inside and outside the kidney.

The nephron is the main working unit of the kidney. There are about a million in each kidney. Each consists of a filter called a glomerulus and a tube called a tubule. The tubule helps the kidney balance body water because some of its sections are permeable to water and certain solutes, some are permeable to just water or solutes, and some are relatively insoluble to water unless occupied by specific water channels.

Water channels that are active in the kidney are CHIP28 (located in that section of the tubule closest to the glomerulus), WCH-CD, MIWC and GLIP, which are all located in the kidney collecting ducts. Researchers carried out structure-function studies on CHIP28. They found that CHIP28 only allowed water to flow through it, its opening being too small for solutes such as urea and ions. This is important because CHIP28 is present in such high numbers in the membranes of certain cells that, should they allow passage of small solutes, the number of solutes passed could damage cell function.

The structures of the CHIP28 water channel is not yet verified, but there seems to be agreement on its general shape. CHIP28 is a protein, a string of amino acid residues located in membranes of specific cells. It has seven regions which do not readily absorb water. These regions may sit coiled within the cell membranes to form seven transmembranes regions. (One model has four of the regions in the membrane as transmembrane helices, another model has six.) Both ends of the CHIP28 sit inside the cell cytoplasm. The basic structural unit of CHIP28, a monomer, is assembled on the cell membranes as a tetramer, i.e., a unit of four monomers. Though CHIP28 forms as a unit of four parts (a tetramer), there is evidence that each of the units (monomers) that comprised the tetramer functions independently, letting water move through narrow pores located within each monomer.

There are other models representing ways CHIP28 might form itself to let water pass through it. The first suggests that water moves through the space formed by the four or more of the transmembrane domains. The second suggests a configuration where the transmembrane helices gather together to form a water pore lined by a beta-sheet formed by amino acids in transmembranes two and five.