Rac GTPases in erythroid biology.
Rac1 and Rac2 GTPases, members of the Rho GTPases family, control actin organization and play distinct and overlapping roles in hematopoietic and mature blood cells of all lineages. Here, we review our findings on the role of Rac GTPases in erythroid cells, by using conditional gene-targeting in mice. Rac1 and Rac2 deficiency causes anemia with reticulocytosis, indicating decreased red blood cell (RBC) survival, altered actin assembly in the erythrocyte membrane skeleton and decreased RBC deformability. On the other hand, Rac1(-/-); Rac2(-/-) megakaryocyte-erythrocyte progenitors demonstrate decreased proliferation in the bone marrow, but increased survival and proliferation in the spleen, indicating that stress erythropoiesis circumvents Rac GTPases deficiency. Further elucidation of the signaling pathways controlled by Rac GTPases in erythroid cells may reveal potential therapeutic targets for diseases characterized by hemolytic anemia and erythropoiesis disorders.
Konstantinidis
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DG
Hematology-Oncology Department, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cancer and Blood Diseases Institute, Cincinnati, 3333, Burnet Avenue, MLC 7015, Cincinnati, OH 45229-3039, USA.
George
A
A
Kalfa
T A
TA
D000740:Anemia / Q000097:blood / Q000235:genetics; D000743:Anemia, Hemolytic / Q000235:genetics; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004907:Erythrocyte Deformability / Q000235:genetics / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011493:Protein Kinase C / Q000097:blood; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000172:deficiency / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D011493:Protein Kinase C; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; D000099291:Adducins