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.