Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency.
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.
Paw
Barry H
BH
Department of Medicine, Division of Hematology-Oncology, Children's Hospital, Boston, Massachusetts, USA.
Davidson
Alan J
AJ
Zhou
Yi
Y
Li
Rong
R
Pratt
Stephen J
SJ
Lee
Charles
C
Trede
Nikolaus S
NS
Brownlie
Alison
A
Donovan
Adriana
A
Liao
Eric C
EC
Ziai
James M
JM
Drejer
Anna H
AH
Guo
Wen
W
Kim
Carol H
CH
Gwynn
Babette
B
Peters
Luanne L
LL
Chernova
Marina N
MN
Alper
Seth L
SL
Zapata
Agustin
A
Wickramasinghe
Sunitha N
SN
Lee
Matthew J
MJ
Lux
Samuel E
SE
Fritz
Andreas
A
Postlethwait
John H
JH
Zon
Leonard I
LI
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*
D001457:Anion Exchange Protein 1, Erythrocyte