Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia.

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Abstract Text:

Huiqing Chen,Anwar A Khan,Fei Liu,Diana M Gilligan,Luanne L Peters,Joanne Messick,Wanda M Haschek-Hock,Xuerong Li,Agnes E Ostafin,Athar H Chishti,

Dematin and adducin are actin-binding proteins of the erythrocyte "junctional complex." Individually, they exert modest effects on erythrocyte shape and membrane stability, and their homologues are expressed widely in non-erythroid cells. Here we report generation and characterization of double knock-out mice lacking beta-adducin and the headpiece domain of dematin. The combined mutations result in altered erythrocyte morphology, increased membrane instability, and severe hemolysis. Peripheral blood analysis shows evidence of severe hemolytic anemia with reduced number of erythrocytes/hematocrit/hemoglobin and an approximately 12-fold increase in the number of circulating reticulocytes. The presence of a variety of misshapen and fragmented erythrocytes correlates with increased osmotic fragility and reduced in vivo life span. Despite the apparently normal protein composition of the mutant erythrocyte membrane, the retention of the spectrin-actin complex in the membrane under low ionic strength conditions is significantly reduced by the double mutation. Atomic force microscopy reveals an increase in grain size and a decrease in filament number of the mutant membrane cytoskeleton, although the volume parameter is similar to wild type erythrocytes. Aggregated, disassembled, and irregular features are visualized in the mutant membrane, consistent with the presence of large protein aggregates. Importantly, purified dematin binds to the stripped inside-out vesicles in a saturable manner, and dematin-membrane binding is abolished upon pretreatment of membrane vesicles with trypsin. Together, these results reveal an essential role of dematin and adducin in the maintenance of erythrocyte shape and membrane stability, and they suggest that the dematin-membrane interaction could link the junctional complex to the plasma membrane in erythroid cells.

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Publishing Authors By Initials

H Chen,AA Khan,F Liu,DM Gilligan,LL Peters,J Messick,WM Haschek-Hock,X Li,AE Ostafin,AH Chishti,

For similar proteins: blood proteins: spectrin research abstracts see: proteins: blood proteins: spectrin research

PUBMED ID PMID:

MEDLINE DATE:

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 4124-35

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 2

MONTH: 12

YEAR: 2006

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Keywords Mesh Terms:

KEYWORDS: Spectrin

MESH TERMS: physiology

Chemical & Substance for Abstract: Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. Information

Substance Name: Spectrin

Registry Number: 12634-43-4

Grant and Affiliation Information for Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia.

AFFILIATION: Department of Pharmacology/Cancer Center, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL075714

ACRONYM: HL

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia Related Publications

• A Presenilin-like protease associated with Plasmodium falciparum micronemes is involved in erythrocyte invasion.
• Ambulatory blood pressure monitoring. A pediatric review.
• BDA-410: a novel synthetic calpain inhibitor active against blood stage malaria.
• Calpain-mediated regulation of platelet signaling pathways.
• Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia.
• Dematin and Adducin Provide a Novel Link between the Spectrin Cytoskeleton and Human Erythrocyte Membrane by Directly Interacting with Glucose Transporter-1.
• Double knockouts reveal that protein tyrosine phosphatase 1B is a physiological target of calpain-1 in platelets.
• Erythrocyte dematin is a candidate gene for Marie Unna hereditary hypotrichosis and related hairloss disorders.
• Giant choroid plexus papilloma of the third ventricle.
• Giant hypothalamic hamartoma and associated seizure types.
• Intravitreal steroids may facilitate treatment of Eales' disease (idiopathic retinal vasculitis): an interventional case series.
• Purification of the NF2 tumor suppressor protein from human erythrocytes.
• Spectrum of childhood poisoning in a tertiary center in the Eastern Saudi Arabia.
• Spontaneous resolution of infantile nephrotic syndrome.
• The effector domain of human Dlg tumor suppressor acts as a switch that relieves autoinhibition of kinesin-3 motor GAKIN/KIF13B.
• The headpiece domain of dematin regulates cell shape, motility, and wound healing by modulating RhoA activation.