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Rho GTPases in erythroid maturation

Kalfa, Theodosia A.; Zheng, Yi

Current Opinion in Hematology: May 2014 - Volume 21 - Issue 3 - p 165–171
doi: 10.1097/MOH.0000000000000032
ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas

Purpose of review: This review summarizes our current understanding of the roles of Rho GTPases in early erythropoiesis, downstream of cytokine signaling, and in terminal erythroblast maturation and enucleation, as master regulators of the cytoskeleton and cytokinesis.

Recent findings: Similarities of structural and signaling requirements of erythroblast enucleation with the cytokinesis process have been confirmed and expanded in the last year, suggesting that enucleation is a form of asymmetric cell division. Myosin, the classic actin partner in cytokinesis, was shown to play an essential role in enucleation. Studies with multispectral high-speed cell imaging in flow demonstrated a sequential process requiring establishment of polarity through a unipolar microtubule spindle in orthochromatic erythroblasts, followed by Rac-directed formation of a contractile actomyosin ring and coalescence of lipid rafts between reticulocyte and pyrenocyte, steps which reiterate the choreography of cytokinesis. mDia2, a Rho effector known to play a role in enucleation, was also found essential for erythroblast cytokinesis as its deficiency in mice caused failure of primitive erythropoiesis and embryonic death.

Summary: Further elucidation of the role of Rho GTPases in the erythroid lineage development may reveal potential targets for improving red blood cell production in vivo and in vitro.

Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Correspondence to Theodosia A. Kalfa, MD, PhD, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7015, Cincinnati, OH 45229-3039, USA. Tel: +1 513 636 0989; fax: +1 513 636 3549; e-mail: theodosia.kalfa@cchmc.org

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins