title: Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency.
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.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Barry H
authors.initials: BH
authors.lastname: Paw
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pratt
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Nikolaus S
authors.initials: NS
authors.lastname: Trede
authors.forename: Alison
authors.initials: A
authors.lastname: Brownlie
authors.forename: Adriana
authors.initials: A
authors.lastname: Donovan
authors.forename: Eric C
authors.initials: EC
authors.lastname: Liao
authors.forename: James M
authors.initials: JM
authors.lastname: Ziai
authors.forename: Anna H
authors.initials: AH
authors.lastname: Drejer
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.forename: Carol H
authors.initials: CH
authors.lastname: Kim
authors.forename: Babette
authors.initials: B
authors.lastname: Gwynn
authors.forename: Luanne L
authors.initials: LL
authors.lastname: Peters
authors.forename: Marina N
authors.initials: MN
authors.lastname: Chernova
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Agustin
authors.initials: A
authors.lastname: Zapata
authors.forename: Sunitha N
authors.initials: SN
authors.lastname: Wickramasinghe
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Lux
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritz
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000595:Amino Acid Sequence; D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency* / Q000235:genetics*; D004920:Erythropoiesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D015027:Zebrafish / Q000097:blood / Q000196:embryology* / Q000235:genetics*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte