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Aquaporins

Aquaporins are molecular water channels that permit rapid transport of water across cellular membranes (1). All mammalian cells are moderately permeable to water even without aquaporins, allowing long-term osmotic equilibration across cell membranes. However, some physiological functions depend on the very rapid water transport mediated by aquaporins.

Aquaporins are particularly important in renal epithelia. Aquaporin-1 is expressed in the renal proximal tubule, where it is vital for so-called 'isosmotic fluid absorption', which allows active sodium transport to drive fluid reabsorption without substantially diluting the luminal fluid (2). Aquaporin-1 is also expressed in the thin descending limb of Henle's loop where it mediates the rapid osmotic water transport necessary for the countercurrent multiplier mechanism (4). Aquaporin-2, -3, and -4 are expressed in the collecting duct epithelial cells (5-7) and mediate osmotic water movement across the apical plasma membrane (aquaporin-2) and the basolateral plasma membrane (aquaporins-3 and -4). Vasopressin controls transepithelial water transport in the renal collecting duct by regulating aquaporin-2 and aquaporin-3 (3, 8, 9).

A major focus of the Epithelial Systems Biology Laboratory (ESBL) is to discover the cellular and molecular mechanisms responsible for vasopressin-mediated regulation of aquaporin-2. The strategy is to use the tools of systems biology to investigate cellular responses. Please go to the 'Systems Biology' link at the left to read about the systems biology methodologies used.

References:

  1. Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: from molecules to medicine Physiol Rev. 2002; 82: 205-44. PMID: 11773613.

  2. Schnermann J, Chou CL, Ma T, Traynor T, Knepper MA, Verkman AS. Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice. Proc Natl Acad Sci USA. 1998; 95: 9660-4. PMID: 9689137.

  3. Terris J, Ecelbarger CA, Nielsen S, Knepper MA. Long-term regulation of four renal aquaporins in rats. Am J Physiol. 1996; 271: F414-22. PMID: 8770174.

  4. Maeda Y, Smith BL, Agre P, Knepper MA. Quantification of Aquaporin-CHIP water channel protein in microdissected renal tubules by fluorescence-based ELISA. J Clin Invest. 1995; 95:422-8. PMID: 7529263.

  5. Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA. 1995; 92:1013-7. PMID: 7532304.

  6. Ecelbarger CA, Terris J, Frindt G, Echevarria M, Marples D, Nielsen S, Knepper MA. Aquaporin-3 water channel localization and regulation in rat kidney. Am J Physiol. 1995; 269:F663-72. PMID: 7503232.

  7. Terris J, Ecelbarger CA, Marples D, Knepper MA, Nielsen S. Distribution of aquaporin-4 water channel expression within rat kidney. Am J Physiol. 1995; 269: F775-85. PMID: 8594871.

  8. DiGiovanni SR, Nielsen S, Christensen EI, Knepper MA. Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. Proc Natl Acad Sci USA. 1994; 91: 8984-8. PMID: 7522327.