A molecular defect in two families with hemolytic poikilocytic anemia: reduction of high affinity membrane binding sites for ankyrin.

Abstract

A B S T R A C T

Defective binding of spectrin to ankyrin in a kindred with recessively inherited hereditary elliptocytosis.

“…The possibility that splenectomy might influence spectrin-IOV interaction was excluded by the finding of a normal binding isotherm of spectrin obtained from a healthy splenectomized subject (not shown). Although the binding curves of control IOV for control spectrin show some variation in different experiments, this may reflect differences in the amount of residual spectrin in the various control IOV preparations, and the variation is similar to that found by Agre et al (17). However, within an experiment, preparations of spectrin from different controls show remarkably similar binding isotherms.…”

“…Deficiencies of band 4.1 (15) and band 4.1 and glycophorin C (16) have also been described in variants of HE. Two families have been described in which the number of effective high affinity ankyrin binding sites in ankyrin-depleted membranes is reduced by half and which is thought to reflect an altered arrangement of band 3 molecules in the membrane (17). Palek and Lux (1) postulate that repeated distortion of erythrocytes with mild membrane skeleton defects in the microcirculation leads to gradual elongation into the typical elliptocytic shape in contrast to normal cells, which realign rapidly in response to stress.…”

Missing band 7 membrane protein in two patients with high Na, low K erythrocytes.

“…Spectrin is either deficient (18) or fails to bind protein 4.1 (19,20) in some patients with spherocytosis, whereas spectrin self-association is defective in pyropoikilocytosis (21). In some individuals with elliptocytosis, there is either a deficiency of protein 4.1 (22) or a reduction of the membrane binding sites for ankyrin (23). In three patients with march hemoglobinuria, Banga and colleagues (24) identified a missing band 7 protein on one-dimensional SDS gel electrophoresis.…”

Unique alpha-spectrin mutant in a kindred with common hereditary elliptocytosis.

“…For example, molecular defects described in kindreds with hereditary elliptocytosis (HE) include a quantitative deficiency of protein 4.1 (4), defective ankyrin-band 3 binding (5), and a number of qualitative defects in spectrin (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Most of alpha-and betaspectrin defects in HE result in diminished self-association of affected spectrin heterodimers (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), leading to reduced formation of higher molecular weight forms of spectrin and, thus, to skeletal instability.…”