Hereditary stomatocytosis and cation-leaky red cells--recent developments.
The hereditary stomatocytoses (HSt) are a diverse group of conditions. Common features include hemolytic anemia, a red cell cation leak and morphological changes, but the severity of the condition can vary enormously. We have previously shown that one form of HSt (cryohydrocytosis), where the monovalent cation leak is increased at low temperature, results from amino acid substitutions in the membrane domain of band 3 (anion exchanger 1, SLC4A1). These substitutions appear to convert band 3 from an anion exchanger into a cation channel. More recently we found that over-hydrated hereditary stomatocytosis (OHSt) results from amino acid substitutions in Rh-associated glycoprotein (RhAG), a putative gas channel protein. Both band 3 and RhAG associate in the red cell membrane to form a macrocomplex that is thought to be involved in red cell gas exchange. In this paper I will review the data that has been published so far on the molecular basis of HSt. I will mention other similar conditions that cause either a cation leak or stomatocytosis or both, and consider the mechanisms of red cell shape change and permeability.
Bruce
Lesley J
LJ
Bristol Institute for Transfusion Sciences, N.H.S. Blood and Transplant, North Bristol Park, Filton, Bristol, BS34 7QH, UK.
D000141:Acidosis, Renal Tubular / Q000097:blood / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000745:Anemia, Hemolytic, Congenital / Q000097:blood* / Q000145:classification / Q000235:genetics; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000838:Anions / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000172:deficiency / Q000502:physiology; D001834:Body Water; D002412:Cations / Q000097:blood*; D002463:Cell Membrane Permeability; D003080:Cold Temperature / Q000009:adverse effects; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D018740:Genetic Heterogeneity; D006801:Humans; D017136:Ion Transport / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D020125:Mutation, Missense; D017354:Point Mutation
D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D001798:Blood Proteins; D002412:Cations; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C498523:RHAG protein, human; C454201:SLC4A1 protein, human; C036860:STOM protein, human