Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Free access | 10.1172/JCI110689

Molecular Defect of Spectrin in Hereditary Pyropoikilocytosis: ALTERATIONS IN THE TRYPSIN-RESISTANT DOMAIN INVOLVED IN SPECTRIN SELF-ASSOCIATION

Jack Lawler, Shih-Chun Liu, and Jiri Palek

Department of Research, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Department of Medicine, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Tufts University School of Medicine, Boston, Massachusetts 02135

Department of Medicine, University of Alabama Medical School, Birmingham, Alabama 35294

Find articles by Lawler, J. in: PubMed | Google Scholar

Department of Research, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Department of Medicine, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Tufts University School of Medicine, Boston, Massachusetts 02135

Department of Medicine, University of Alabama Medical School, Birmingham, Alabama 35294

Find articles by Liu, S. in: PubMed | Google Scholar

Department of Research, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Department of Medicine, St. Elizabeth's Hospital of Boston, Boston, Massachusetts 02135

Tufts University School of Medicine, Boston, Massachusetts 02135

Department of Medicine, University of Alabama Medical School, Birmingham, Alabama 35294

Find articles by Palek, J. in: PubMed | Google Scholar

Published November 1, 1982 - More info

Published in Volume 70, Issue 5 on November 1, 1982
J Clin Invest. 1982;70(5):1019–1030. https://doi.org/10.1172/JCI110689.
© 1982 The American Society for Clinical Investigation
Published November 1, 1982 - Version history
View PDF
Abstract

In hereditary pyropoikilocytosis (HPP) the erythrocyte membrane skeleton exhibits mechanical instability that can be correlated to defective self-association of spectrin heterodimers. To detect structural changes in the functional domains of HPP spectrin we have examined the peptide pattern produced by limited tryptic digestion of spectrin extracts from two families that contain three HPP patients. Limited tryptic digestion of all three HPP patients revealed a similar and reproducible decrease in the staining intensity of an 80,000-, and 22,000-, and an 88,000-dalton polypeptide with a concomitant increase in a 74,000- and a 90,000-dalton polypeptide as compared with controls. Only changes in the 80,000-, and 74,000-, and 22,000-dalton polypeptides could be correlated to defective spectrin self-association and the amount of spectrin dimers in 0°C extracts of the HPP patients and their affected kindred. Similar results were obtained when the tryptic digests were analyzed by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the affected 74,000- and 80,000-dalton polypeptides focusing into multiple spots ranging in isoelectric point from 5.3-5.4. When HPP spectrin dimers and tetramers were separated and subjected to trypsin digestion, changes in the 80,000-, 74,000-, and 22,000-dalton polypeptides were found predominantly in the spectrin dimer pool. Similar results were obtained for spectrin from two of the probands' mother, whom we have identified as an HPP carrier. We conclude that these HPP patients contain a population of normal, (principally tetrameric) and mutant (principally dimeric) spectrin. The latter is characterized by a defective spectrin dimer self-association due to conformational changes that affect the 80,000-dalton domain.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 1019
page 1019
icon of scanned page 1020
page 1020
icon of scanned page 1021
page 1021
icon of scanned page 1022
page 1022
icon of scanned page 1023
page 1023
icon of scanned page 1024
page 1024
icon of scanned page 1025
page 1025
icon of scanned page 1026
page 1026
icon of scanned page 1027
page 1027
icon of scanned page 1028
page 1028
icon of scanned page 1029
page 1029
icon of scanned page 1030
page 1030
Version history
  • Version 1 (November 1, 1982): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts