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

Steven Goodman, K. A. Shiffer, L. Casoria, M. E. Eyster

Research output: Contribution to journalArticle

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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
StatePublished - Jan 1 1982
Externally publishedYes

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Hereditary Spherocytosis
Spectrin
Erythrocyte Membrane
Skeleton
Membranes
Defects
Proteins
Actins
Carrier Proteins
Erythrocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis. / Goodman, Steven; Shiffer, K. A.; Casoria, L.; Eyster, M. E.

In: Blood, Vol. 60, No. 3, 01.01.1982, p. 772-784.

Research output: Contribution to journalArticle

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N2 - 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.

AB - 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.

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