Feb 21, 2013

Hematopoietic protein-1 regulates the actin membrane skeleton and membrane stability in murine erythrocytes

PloS One
Maia M ChanBrian M Iritani

Abstract

Hematopoietic protein-1 (Hem-1) is a hematopoietic cell specific member of the WAVE (Wiskott-Aldrich syndrome verprolin-homologous protein) complex, which regulates filamentous actin (F-actin) polymerization in many cell types including immune cells. However, the roles of Hem-1 and the WAVE complex in erythrocyte biology are not known. In this study, we utilized mice lacking Hem-1 expression due to a non-coding point mutation in the Hem1 gene to show that absence of Hem-1 results in microcytic, hypochromic anemia characterized by abnormally shaped erythrocytes with aberrant F-actin foci and decreased lifespan. We find that Hem-1 and members of the associated WAVE complex are normally expressed in wildtype erythrocyte progenitors and mature erythrocytes. Using mass spectrometry and global proteomics, Coomassie staining, and immunoblotting, we find that the absence of Hem-1 results in decreased representation of essential erythrocyte membrane skeletal proteins including α- and β- spectrin, dematin, p55, adducin, ankyrin, tropomodulin 1, band 3, and band 4.1. Hem1⁻/⁻ erythrocytes exhibit increased protein kinase C-dependent phosphorylation of adducin at Ser724, which targets adducin family members for dissociation from spectrin an...Continue Reading

  • References52
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References

Mentioned in this Paper

5-(6)-carboxyfluorescein diacetate succinimidyl ester
Metabolic Process, Cellular
Real-Time Polymerase Chain Reaction
Schistocyte
Flow Cytometry
Schistocyte Count
Anion Exchange Protein 1, Erythrocyte
Biochemical Pathway
Dacryocyte Analysis
ABI2 gene

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