More than just water channels: unexpected cellular roles of aquaporins

Abstract

Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol. AQPs are expressed in many fluid-transporting tissues, such as kidney tubules and glandular epithelia, as well as in non-fluid-transporting tissues, such as epidermis, adipose tissue and astroglia. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.

Functions of aquaporins in the eye

“…A serum immunoglobulin was discovered in NMO subjects, but not in MS or normal subjects, which was subsequently found to target AQP4 (Lennon et al, 2004 and2005). These findings firmly distinguish NMO and MS as separate disease entities.…”

“…Much of our knowledge of AQP physiology has come from phenotype analysis of mice lacking AQPs (reviewed in Verkman, 2005). Some AQPs roles were predictable, such as their function in transepithelial fluid absorption and secretion, while others were unexpected, such as their involvement in cell migration and neural signaling transduction, and aquaglyceroporin involvement in cell proliferation and skin and fat metabolism.…”

“…It has also been proposed that AQP0 acts as a scaffold for organizing gamma-crystallins in lens fibers (Fan et al, 2004). Electron crystallography suggested that AQP0 forms not only water pores, but also 11-13 nm 'thin lens junctions', providing evidence for AQP0 involvement in fiber-fiber adhesion (Gonen et al, 2004;2005). The crystal structure also revealed that AQP0 exists in two configurations: a so-called junctional conformation, which forms 'thin lens junctions', and a non-junctional conformation, which forms the water pore (Harries et al, 2004;Gonen et al, 2004).…”

Aquaporins in spermatozoa and testicular germ cells: identification and potential role

“…It is known that various AQPs are involved in transport of small molecules besides water, such as urea, chloride, heavy metal salts, ammonia, hydrogen peroxide and others, and thus may have unexpected cellular roles [12,82]. A role of AQP11 in the efflux of water and nonmetabolizable substances across membranes of organelles has been proposed, although the identities of the transported molecules have proved elusive [83].…”

“…Aquaporins (AQPs) are water-selective channels which enable a 10-100-fold higher capacity for water transport across plasma membranes (see Agre et al [10]). Among mammalian cells, 13 members of the AQP family have so far been identified, each being predominantly located in different tis-npg sues, and most individual cell types having more than one AQP family member [11,12]. The work on sperm AQP in our laboratory was prompted by the normal existence of osmotic challenges to spermatozoa in the male and female reproductive tracts and the physiological importance of sperm volume regulation.…”