0 avis
Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect
Archive ouverte
Edité par CCSD ; Nature Publishing Group -
International audience. Aquaporins (AQPs) are a family of evolutionarily conserved membrane proteins that facilitate the transport mainly of water but also of some other small molecules across the cell membrane 1,2 and between organelles. 3,4 Multiple (patho)physiologic functions have been attributed to AQPs. These include the urine-concentrating mechanism, epithelial fluid secretion, cell migration, mediation of cerebral edema, and neural signal transduction (reviewed in ref. 5). AQPs have six transmembrane domains, the NH2-and COOH-terminal domains being in the cytoplasm. The channel pore is made of two highly conserved short hydrophobic regions with a typical asparagine-prolinealanine (NPA) motif. 6,7 To date, 13 AQP family members (AQP0-12) have been identified in various mammalian tissues. 2 AQPs are classified, according to their sequence homology and permeability, into three subfamilies: (i) the water-specific "classical" AQPs, (ii) the aquaglyceroporins, and (iii) the unorthodox AQPs. 4 , 8-11 The aquaglyceroporin subfamily transports glycerol in addition to water because of the presence of an aspartic residue near the second NPA box, resulting in expansion of the pore to accept a larger molecule such as glycerol. The four subtypes of the aquaglyceroporin subfamily are: AQP3, AQP7, AQP9, and AQP10 (reviewed in refs. 9,10). Unorthodox AQPs are highly similar to the other AQP subclasses, but additional three-dimensional structure analyses are required for a better understanding of the pore structure of this subclass. 7 Aquaporin 7 (AQP7; MIM602974) was previously referred to as "aquaporin adipose" because it was originally identified in human adipose tissue. 12 Subsequently, other researchers found AQP7 expression in testis and renal proximal tubule cells. 13,14 The various AQP7 mouse models that were developed (for a phenotype overview, see Supplementary Table S1 online) showed a role for AQP7 in controlling fat and in glucose metabolism. 15-17 AQP7-knockout mice were shown to develop obesity and insulin resistance, with excess glycerol concentrations in the adipocytes. In addition, it was shown that these mice have reduced water permeability in the renal proximal straight tubule brush border membrane and a marked elevation of glycerol in the urine, possibly indicating the presence of a novel glycerol reabsorption pathway in the proximal straight tubules.
Consulter en ligne
Suggestions
Du même auteur
