Disease relevance of Aqp6

• Moreover, rats with lithium-induced nephrogenic diabetes insipidus had a threefold increase in both AQP6 protein and mRNA expression [1].

High impact information on Aqp6

• When expressed in Xenopus laevis oocytes, AQP6 exhibits low basal water permeability; however, when treated with the known water channel inhibitor, Hg2+, the water permeability of AQP6 oocytes rapidly rises up to tenfold and is accompanied by ion conductance [2].
• Although mammalian aquaporins were believed to be located in plasma membranes, rat AQP6 is restricted to intracellular vesicles in renal epithelia [2].
• Uniquely, all known mammalian orthologs of AQP6 have an asparagine residue (Asn-60) at the position corresponding to Gly-57 [3].
• Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution [3].
• In collecting duct, AQP6 resides in intracellular membrane vesicles in apical, mid, and basolateral cytoplasm of type A intercalated cells, but was not observed in the plasma membrane [4].

Biological context of Aqp6

• Moreover, our studies predict that AQP6 participates in distinct physiological functions such as glomerular filtration, tubular endocytosis, and acid-base metabolism [4].
• In contrast, administration of NH(4)Cl in the drinking water for 2 wk (free access to water) revealed a significant increase in AQP6 protein abundance (194 +/- 9% of control), but this was associated with increased water intake [1].
• Thus AQP6 may contribute to maintenance of acid-base homeostasis and water balance [1].

Anatomical context of Aqp6

• At pH less than 5.5, anion conductance is rapidly and reversibly activated in AQP6 oocytes [2].
• Here we show that AQP6 is localized exclusively in intracellular membranes in renal epithelia [4].
• By using a polyclonal antibody to the C terminus of AQP6, immunoblots revealed a major 30-kDa band in membranes from rat renal cortex and medulla [4].
• In glomeruli, AQP6 is present in membrane vesicles within podocyte cell bodies and foot processes [4].
• In proximal tubules, AQP6 is also abundant in membrane vesicles within the subapical compartment of segment 2 and segment 3 cells, but was not detected in the brush border or basolateral membranes [4].

Associations of Aqp6 with chemical compounds

• Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63 [5].

Other interactions of Aqp6

• Results from the study demonstrate that water channels AQP1 and AQP6, and the heterotrimeric Go protein are associated with SVs and participate in their swelling [6].
• AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined [7].

Analytical, diagnostic and therapeutic context of Aqp6

• Sequential ultracentrifugation of rat kidney homogenates confirmed that AQP6 resides predominantly in vesicular fractions, and immunohistochemical and immunoelectron microscopic studies confirmed that >98% of AQP6 is located in intracellular membrane vesicles [4].
• Immunohistochemistry revealed increased IC AQP6 labeling in alkali-loaded rats but not in acid-loaded rats [1].
• No glomerular expression of AQP6 mRNA was confirmed by RT-PCR using total RNA extracted from the glomeruli [8].
• In situ hybridization demonstrated significant signals for AQP6 mRNA along the outer and inner medullary collecting ducts [8].

References