Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

S. R. Goodman, K. A. Shiffer, L. Casoria, M. E. Eyster

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    55 Scopus citations

    Abstract

    We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin-protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds ~63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the ~37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer-heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.

    Original languageEnglish (US)
    Pages (from-to)772-784
    Number of pages13
    JournalBlood
    Volume60
    Issue number3
    DOIs
    StatePublished - 1982

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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