Liu S C, Palek J, Prchal J T
Proc Natl Acad Sci U S A. 1982 Mar;79(6):2072-6. doi: 10.1073/pnas.79.6.2072.
We examined erythrocytes from 18 patients with hereditary elliptocytosis. Spectrin from eight patients (referred to as type 1) was defective in dimer-dimer association as demonstrated in two ways. First, there was an increased amount of spectrin dimer with a concomitant decrease in tetramer as measured in erythrocyte membrane preparations extracted at 0 degrees 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%). Second, 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, we postulate that the defective spectrin dimer-dimer association in type 1 diminishes actin crosslinking and thus is responsible for membrane skeletal instability. A defective protein-protein association in type 2, however, remains to be identified.
我们检查了18例遗传性椭圆形红细胞增多症患者的红细胞。8例患者（称为1型）的血影蛋白在二聚体-二聚体结合方面存在缺陷，这通过两种方式得以证明。首先，在0摄氏度低盐条件下提取的红细胞膜制剂中，血影蛋白二聚体的量增加，同时四聚体减少（血影蛋白二聚体占血影蛋白总量的15%-33%，而正常范围为3%-7%）。其次，血影蛋白二聚体-二聚体结合的平衡常数在溶液和原位膜中均降低。其余10例患者（称为2型）的血影蛋白显示出正常的二聚体-二聚体结合。通过Triton X-100提取两种类型遗传性椭圆形红细胞增多症的血影所产生的膜骨架，在机械摇动时不稳定。由于血影蛋白四聚体而非二聚体可以交联肌动蛋白，我们推测1型中存在缺陷的血影蛋白二聚体-二聚体结合减少了肌动蛋白交联，因此导致了膜骨架的不稳定。然而，2型中存在缺陷的蛋白质-蛋白质结合仍有待确定。
