The 2003 Nobel Prize in Chemistry was awarded to American PhysiologicalSociety member Peter C. Agre from Johns Hopkins School of Medicinefor being the first to identify and characterize water channels(photo courtesy of Hans Mehlin, Nobel e-Museum). This pivotalwork of Dr. Agre and collaborators began in the search for thered cell protein responsible for Rh immunoreactivity. In thesestudies, a protein contaminant was found that was isolated andpurified and then cloned and characterized (1, 4, 5). Thesestudies demonstrated that this protein is highly expressed notonly in red cells but also in the renal proximal tubule andthe descending limb of the loop of Henle and that it mediatesthe transport of water (1, 5). We now refer to this proteinas aquaporin-1. Agre and collaborators went on to demonstratethat humans with mutations in aquaporin-1 cannot concentratetheir urine fully (2). Since then, an entire family of waterchannels have been identified, cloned, and characterized. Theseseminal studies of Agre and collaborators have thus resultedin an explosion of knowledge regarding water movement acrosscell membranes and, in particular, how water channels contributeto urinary concentration. The extensive contributions of theAgre laboratory have been reviewed in greater detail elsewhere(3).
Denker BM, Smith BL, Kuhajda FP, and Agre P. Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J Biol Chem 263: 1563415642, 1988.[Abstract/Free Full Text]
King LS, Choi M, Fernandez PC, Cartron JP, and Agre P. Defective urinary concentrating ability due to a complete deficiency of aquaporin-1. N Engl J Med. 345: 175179, 2001.[Free Full Text]
Knepper MA and Nielsen S. Peter Agre, 2003 Nobel Prize winner in chemistry. J Am Soc Nephrol 15: 10931095, 2004.[Abstract/Free Full Text]
Preston GM and Agre P. Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. Proc Natl Acad Sci USA 88: 1111011114, 1991.[Abstract]
Preston GM, Carroll TP, Guggino WB, and Agre P. Appearance of water channels in xenopus oocytes expressing red cell CHIP28 protein. Science 256: 385387, 1992.