Defective spectrin dimer-dimer association with hereditary elliptocytosis.

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Abstract
Erythrocytes were examined from 18 patients with hereditary elliptocytosis. Spectrin from 8 patients (referred to as type 1) was defective in dimer-dimer association as demonstrated in 2 ways. There was an increased amount of spectrin dimer with a concomitant decrease in tetramer as measured in erythrocyte membrane preparations extracted at 0.degree. C under low-salt conditions (the amount of spectrin dimer was 15-33% of total spectrin species compared with a normal range of 3-7%). The equilibrium constants of spectrin dimer-dimer association were decreased in both solution and in situ membrane. Spectrin from the remaining 10 patients (referred to as type 2) showed normal dimer-dimer association. Membrane skeletons, produced from ghosts of both types of hereditary elliptocytosis by Triton X-100 extraction, were unstable when mechanically shaken. Because spectrin tetramers, but not dimers, can crosslink actin, the defective spectrin dimer-dimer association in type 1 may dimish actin crosslinking and thus be responsible for membrane skeletal instability. A defective protein-protein association in type 2 remains to be identified.