ZFIN ID: ZDB-PUB-001107-2
Hereditary spherocytosis in zebrafish riesling illustrates evolution of erythroid ß-spectrin structure, and function in red cell morphogenesis and membrane stability
Liao, E.C., Paw, B.H., Peters, L.L., Zapata, A., Pratt, S.J., Do, C.P., Lieschke, G., and Zon, L.I.
Date: 2000
Source: Development (Cambridge, England) 127(23): 5123-5132 (Journal)
Registered Authors: Do, Cuong, Liao, Eric, Lieschke, Graham J., Paw, Barry, Pratt, Stephen J., Zon, Leonard I.
Keywords: erythroid b-spectrin; sptb; riesling; hereditary spherocytosis; apoptosis; marginal band; pleckstrin homology domain; hematopoiesis; zebrafish
MeSH Terms: Amino Acid Sequence; Animals; Apoptosis; Base Sequence; DNA, Complementary (all 18) expand
PubMed: 11060238
FIGURES   (current status)
ABSTRACT
Spectrins are key cytoskeleton proteins with roles in membrane integrity, cell morphology, organelle transport and cell polarity of varied cell types during development. Defects in erythroid spectrins in humans result in congenital hemolytic anemias with altered red cell morphology. Although well characterized in mammals and invertebrates, analysis of the structure and function of non-mammalian vertebrate spectrins has been lacking. The zebrafish riesling (ris) suffers from profound anemia, where the developing red cells fail to assume terminally differentiated erythroid morphology. Using comparative genomics, erythroid b-spectrin (sptb) was identified as the gene mutated in ris. Zebrafish Sptb shares 62.3% overall identity with the human ortholog and phylogenetic comparisons suggest intragenic duplication and divergence during evolution. Unlike the human and murine orthologs, the pleckstrin homology domain of zebrafish Sptb is not removed in red cells by alternative splicing. In addition, apoptosis and abnormal microtubule marginal band aggregation contribute to hemolysis of mutant erythrocytes, which are features not present in mammalian red cells with sptb defects. This study presents the first genetic characterization of a non-mammalian vertebrate sptb and demonstrates novel features of red cell hemolysis in non-mammalian red cells. Further, we propose that the distinct mammalian erythroid morphology may have evolved from specific modifications of Sptb structure and function.
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