ZFIN ID: ZDB-PUB-030408-10
Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency
Paw, B.H., Davidson, A.J., Zhou, Y., Li, R., Pratt, S.J., Lee, C., Trede, N.S., Brownlie, A., Donovan, A., Liao, E.C., Ziai, J.M., Drejer, A.H., Guo, W., Kim, C.H., Gwynn, B., Peters, L.L., Chernova, M.N., Alper, S.L., Zapata, A., Wickramasinghe, S.N., Lee, M.J., Lux, S.E., Fritz, A., Postlethwait, J.H., and Zon, L.I.
Date: 2003
Source: Nature Genetics 34(1): 59-64 (Journal)
Registered Authors: Brownlie, Alison J., Davidson, Alan, Donovan, Adriana, Fritz, Andreas, Guo, Wen, Lee, Charles, Liao, Eric, Paw, Barry, Postlethwait, John H., Pratt, Stephen J., Trede, Nick, Zhou, Yi, Ziai, James, Zon, Leonard I.
Keywords: none
MeSH Terms: Amino Acid Sequence; Anemia, Dyserythropoietic, Congenital/genetics; Animals; Animals, Genetically Modified; Anion Exchange Protein 1, Erythrocyte/deficiency* (all 20) expand
PubMed: 12669066 Full text @ Nat. Genet.
ABSTRACT
Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.
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