Phosphoinositide metabolism in hereditary ovalocytic red blood cell membranes
ABSTRACT Metabolic depletion of hereditary ovalocytes leads, similar to normal red cells, to decreased intracellular concentrations of ATP and GSH as well as degradation of the phosphoinositides to phosphatidylinositol and diacylglycerol. In contrast to normal red cells, however, loss of ATP does not induce any gross shape transformations; even after extensive depletion the ovalocytes retain their initial elongated stomatocytic character. The mechanical properties of hereditary ovalocytes are associated with a deletion of nine amino acid residues in band 3. Since the deletion appears to increase the stiffness of a normally flexible region of band 3, connecting the N-terminal cytoplasmic domain with the membrane spanning domain, our results indicate that shape changes require a flexible attachment of the cytoskeleton to the membrane-spanning band 3. The results also imply that metabolism of phosphoinositide cannot be the only determinant of cell shape, as suggested by the bilayer-couple hypothesis, but also other factors are involved in metabolically induced shape transformations.
Full-textDOI: · Available from: Lars Backman, Jun 24, 2015
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ABSTRACT: Erythrocytes suspended at a low hematocrit in a non-buffered isotonic saline change from biconcave discs to spheres between glass surfaces of a slide and of a coverslip with the echinocyte as an intermediate. A pH increase is a major factor responsible for this disc-sphere transformation or glass effect. It is also observed between surfaces made of various polymers and of mica provided that the distance between them is controlled (0.1 mm). The glass effect is antagonized by serum, plasma, serum albumin, ammonium salts and CO2. It is not observed above a 1-2% hematocrit, but is enhanced by gamma-globulins. The sites of reappearance of the spicules are the same and the order of their disappearance is the inverse of the order of their reappearance during the repetitive cycle of the disc-sphere transformation and reversal when a small glass rod is alternatively approached near a site on the erythrocyte surface and withdrawn. A mechanism of erythrocyte shape control has been previously hypothesized in which Band 3 (AE1), the anion exchange protein, plays a central role. Specifically, decrease and increase of the ratio of its outward-facing conformation (Band 3o) and inward-facing conformation (Band 3i) contract and relax the membrane skeleton, promoting the echinocytosis and stomatocytosis, respectively. The Band 3o/Band 3i equilibrium ratio is determined by the Donnan equilibrium ratio of Cl-, HCO3- and H+ (r=Cl(i)-/Cl(o)-=HCO3i-/HCO3o-=Ho+/Hi+), increasing with it. The mechanism could explain by a change of the Donnan ratio the above observations with the assumptions that polymers are permeable to CO2 and that an unstirred layer slows the propagation of the change occurring at the site of approach of the glass rod to peripheral sites. The presence of HCO3- in serum or plasma may be the basis for the absence of the glass effect in these fluids.Journal of Theoretical Biology 04/2005; 233(1):127-35. DOI:10.1016/j.jtbi.2004.09.013 · 2.30 Impact Factor