Ultrastructural Changes of Erythrocyte Membrane Skeletons in Chorea-Acanthocytosis and McLeod Syndrome Revealed by the Quick-Freezing and Deep-Etching Method

Abstract

The shapes of acanthocytic erythrocytes have been thought to be related to changes of the organization of the membrane components. In this study, acanthocytes from a patient with chorea-acanthocytosis and a patient with McLeod syndrome were examined. These acanthocytes had a greater tendency to form spikes than normal erythrocytes in an incubation culture system, indicating their weakness against membrane tension. The membrane skeletons of erythrocytes from both patients were examined by our erythrocyte-splitting method followed by the quick-freezing and deep-etching method. The ultrastructural organization of the membrane skeletons was heterogeneous even in individual erythrocytes, indicating regional changes in the compactness of their meshworks. In the process of erythrocyte splitting, some erythrocyte membranes became reversed and protruded into the cytoplasmic side. In these regions, there were fewer filamentous structures. The focal membrane skeletal changes, which are probably one of the factors that induce the phenotype of an acanthocytic erythrocyte, were demonstrated for the first time by this method.

Erythrocyte membrane changes of chorea-acanthocytosis are the result of altered Lyn kinase activity

“…Condensed skeletal structures around protrusions and a less filamentous structure in some large membrane patches indicate a perturbation of membrane cytoskeleton network associated with the membrane protrusions that characterize acanthocytes. 8 These structural data were also supported by the observation that ChAc patients have a fraction of dense RBCs containing acanthocytes with a reduced cell K ϩ content compared with normal controls. 9 RBCs from ChAc patients did not show overall abnormalities in RBC membrane protein composition and content, although there is accumulating evidence for neuroacanthocytosis-specific abnormalities in band 3 structure and function.…”

“…Thus, we propose that in ChAc RBCs the "Lyn storm" might affect the organization of the complexes bridging the membrane to the cytoskeleton, most likely by inducing abnormal protein interactions through the opening of SH2 binding sites in a Syk-independent manner. This might result in the heterogeneous distribution of the cytoskeleton as observed in electron microscopy studies, 8 and may be similar to the concentration of Lyn in plasma membrane patches of activated platelets, adjacent to granules. 42,43 In addition, abnormal Lyn phosphorylation might also contribute to altered vesiculation of ChAc RBCs.…”

Acanthocytosis and neurological disorders

“…Studies of erythrocyte membrane lipid composition in European neuroacanthocytosis cases have mostly been normal [19,20,43], whereas Japanese patients have been reported to have altered phospholipid content, increased palmitic acid and decreased stearic acid [45,54]. Ultrastructural abnormalities of the membranous skeleton have been observed using freeze-fracture electron microscopy [64,66]. Alterations in the degree of phosphorylation of membrane proteins and abnormal flux of chloride or sulphate anions have also been reported [43].…”

“…Focal changes in the cytoskeletal structure are probably responsible for acanthocyte transformation [26,64].…”

Alterations of Red Cell Membrane Properties in Nneuroacanthocytosis

“…Alterations of the cytoskeleton have already been described for ChAc erythrocytes. An enrichment of spectrin in the thorns of acanthocytes was observed by scanning and transmission electron microscopy [25,26]. In this respect it is interesting that spectrin has been implicated to be necessary for the regeneration of the normal discoid shape after artificially induced echinocytosis.…”