Tags

Type your tag names separated by a space and hit enter

Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells.
J Clin Invest. 1976 Oct; 58(4):955-63.JCI

Abstract

Irreversibly sickled cells (ISC's) are circulating erythrocytes in patients with sickle cell disease that retain a sickled shape even when oxygenated. Evidence points to a membrane defect that prevents the return of these cells to the normal biconcave shape. The erythrocyte membrane protein spectrin is believed to help control erythrocyte shape and deformability. Recent studies suggest that normally spectrin and an erythrocyte actin form a self-supporting, fibrillar, lattice-like network on the cytoplasmic membrane surface. When normal erythrocyte ghosts are extracted with Triton X-100 all the integral membrane proteins and most of the membrane lipids are removed, leaving a ghost-shaped residue composed principally of spectrin and actin. We concentrated ISC's from patients with sickle cell anemia and compared the morphology and protein composition of ghosts and Triton-extracted ghost residues prepared from these ISC's with similar preparations of reversibly sickable cells and normal cells. (a) Many ISC's formed ISC-shaped ghosts. (b) All ISC-shaped ghosts formed ISC-shaped Triton residues. (c) Spectrin, erythrocyte actin (Band 5), an unidentified Band 3 component, and Band 4.1 were the major protein components of the Triton residues. All membrane-associated sickle hemoglobin was removed by the Triton treatment. (d) No ISC-shaped ghosts or ISC-shaped Triton residues were formed when deoxygenated, sickled RSC's were lysed or Triton-extracted. ISC-shaped ghosts and Triton residues were never formed from normal cells. These observations suggest that a defect of the "spectrin-actin lattice" may be the primary abnormality of the ISC membrane. Since ISC's are rigid cells, the data support the postulate that spectrin is a major determinant of membrane deformability. Finally, they provide direct evidence that spectrin is important in determining erythrocyte shape.

Links

PMC Free PDF
PMC Free Full Text

Authors

Lux SE
No affiliation info available
John KM
No affiliation info available
Karnovsky MJ
No affiliation info available

MeSH

ActinsAnemia, Sickle CellErythrocytes, AbnormalPolyethylene Glycols

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

965498

Citation

Lux, S E., et al. "Irreversible Deformation of the Spectrin-actin Lattice in Irreversibly Sickled Cells." The Journal of Clinical Investigation, vol. 58, no. 4, 1976, pp. 955-63.
Lux SE, John KM, Karnovsky MJ. Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells. J Clin Invest. 1976;58(4):955-63.
Lux, S. E., John, K. M., & Karnovsky, M. J. (1976). Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells. The Journal of Clinical Investigation, 58(4), 955-63.
Lux SE, John KM, Karnovsky MJ. Irreversible Deformation of the Spectrin-actin Lattice in Irreversibly Sickled Cells. J Clin Invest. 1976;58(4):955-63. PubMed PMID: 965498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells. AU - Lux,S E, AU - John,K M, AU - Karnovsky,M J, PY - 1976/10/1/pubmed PY - 1976/10/1/medline PY - 1976/10/1/entrez SP - 955 EP - 63 JF - The Journal of clinical investigation JO - J Clin Invest VL - 58 IS - 4 N2 - Irreversibly sickled cells (ISC's) are circulating erythrocytes in patients with sickle cell disease that retain a sickled shape even when oxygenated. Evidence points to a membrane defect that prevents the return of these cells to the normal biconcave shape. The erythrocyte membrane protein spectrin is believed to help control erythrocyte shape and deformability. Recent studies suggest that normally spectrin and an erythrocyte actin form a self-supporting, fibrillar, lattice-like network on the cytoplasmic membrane surface. When normal erythrocyte ghosts are extracted with Triton X-100 all the integral membrane proteins and most of the membrane lipids are removed, leaving a ghost-shaped residue composed principally of spectrin and actin. We concentrated ISC's from patients with sickle cell anemia and compared the morphology and protein composition of ghosts and Triton-extracted ghost residues prepared from these ISC's with similar preparations of reversibly sickable cells and normal cells. (a) Many ISC's formed ISC-shaped ghosts. (b) All ISC-shaped ghosts formed ISC-shaped Triton residues. (c) Spectrin, erythrocyte actin (Band 5), an unidentified Band 3 component, and Band 4.1 were the major protein components of the Triton residues. All membrane-associated sickle hemoglobin was removed by the Triton treatment. (d) No ISC-shaped ghosts or ISC-shaped Triton residues were formed when deoxygenated, sickled RSC's were lysed or Triton-extracted. ISC-shaped ghosts and Triton residues were never formed from normal cells. These observations suggest that a defect of the "spectrin-actin lattice" may be the primary abnormality of the ISC membrane. Since ISC's are rigid cells, the data support the postulate that spectrin is a major determinant of membrane deformability. Finally, they provide direct evidence that spectrin is important in determining erythrocyte shape. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/965498/Irreversible_deformation_of_the_spectrin_actin_lattice_in_irreversibly_sickled_cells_ L2 - https://doi.org/10.1172/JCI108549 DB - PRIME DP - Unbound Medicine ER -