title: The curious genomic path from leaky red cell to nephrotic kidney.
abstract: The human red cell has proved to be an invaluable model cell for the study of many aspects of membrane structure and function. It has a series of transport pathways which mediate the movements of the univalent cations Na and K, which are either identical or similar to systems in other human tissues, including the human kidney. The balance between the energy-consuming NaK pump and a 'passive leak' component maintains a net deficit of cations within the cell, which defends the cell volume against osmotic swelling. There exist a series of dominantly inherited human red cell conditions, gathered under the generic title 'hereditary stomatocytoses', in which the so-called 'passive leak' to Na and K is pathologically increased. In the more severe variants this compromises the integrity of the cell and the patients suffer haemolytic anaemia. Some less severe variants present with pseudohyperkalaemia caused by loss of K from red cells on storage of blood at room temperature. The most severe variants show a deficiency in a widely distributed 'raft' protein known as stomatin. The stomatin protein is homologous to the 'podocin' protein, the gene for which is mutated in a recessively inherited form of nephrotic syndrome. Among other possible functions, both proteins could be involved in the trafficking of membrane proteins to and from the plasma membrane.
authors.affiliation: Department of Medicine, University College London, Rayne Institute, London, UK. g.stewart@ucl.ac.uk
authors.forename: G W
authors.initials: GW
authors.lastname: Stewart
authors.forename: B
authors.initials: B
authors.lastname: Fricke
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism; D016678:Genome; D006801:Humans; D017136:Ion Transport; D007668:Kidney / Q000737:chemistry; D008565:Membrane Proteins; D009154:Mutation; D009404:Nephrotic Syndrome / Q000235:genetics*; D011188:Potassium; D012964:Sodium / Q000378:metabolism; D013696:Temperature
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; C036860:STOM protein, human; D012964:Sodium; D011188:Potassium