Physiology and pathophysiology of aquaporins

The biophysical properties of water-filled pores in biological membranes have been studied for decades, and this has cumulated in an accurate description of water channel properties [1]. In spite of all this knowledge, the molecular identification of water channels resulted from a serendipitous discovery. Denker et al. [2] copurified a 28-kD protein together with a 32-kD Rhesus antigen from human red blood cells, and this discovery led to the cloning of the first molecular water channel, CHIP28 [3]. CHIP28 appeared to be a member of the major intrinsic protein (MIP) family of intrinsic membrane proteins, named after the first cloned protein of this family, the major intrinsic protein of lens fibre cells [4]. The molecular fingerprint of MIP family members consists of two repeats, presumably the result of an ancient gene duplication event [5]. Each repeat is characterized by a very conserved region in which an NPA box (asparagine–proline–alanine) is unchanged from bacteria to mammals (Fig.1). Owing to this property, new family members were discovered by homology cloning using reverse transcription–polymerase chain reaction (RT–PCR) and primers corresponding to these conserved sequences [6–12]. It is now clear that genes coding for MIP proteins are ubiquitous in nature. For the functional characterization of water channels, theXenopus oocyte expression system has played a dominant role, merely because the osmotic swelling test of oocytes expressing water channels is of appealing simplicity. For MIP family members that were proven to be water selective, a new more appropriate name was chosen and since then water channels discovered in mammalian tissues have been rebaptized as aquaporins 0 to 5, in the rank order of their discovery [13]. In this review, we will focus on publications that appeared in 1994 and 1995 and we restrict ourselves to mam-malian aquaporins. A number of excellent reviews on water channels have recently been published, reflecting the excitement which surrounds the discovery of aquaporins and their role in water homeostasis of the body [14–17].