Erythroblast enucleation

Abstract

Even though the production of orthochromatic erythroblasts can be scaled up to fulfill clinical requirements, enucleation remains one of the critical rate-limiting steps in the production of transfusable red blood cells. Mammalian erythrocytes extrude their nucleus prior to entering circulation, likely to impart flexibility and improve the ability to traverse through capillaries that are half the size of erythrocytes. Recently, there have been many advances in our understanding of the mechanisms underlying mammalian erythrocyte enucleation. This review summarizes these advances, discusses the possible future directions in the field, and evaluates the prospects for improved ex vivo production of red blood cells.

Figure 1

Key events in cytokinesis and enucleation. Even though the final stages of cytokinesis and enucleation are both driven by vesicle trafficking, the preceding events are substantially different between the two processes.

Figure 2

Model of enucleation. A schematic representation of the enucleation process in mammals is shown. Yellow arrows denote the direction of force applied over the nucleus by actin cytoskeleton. Blue arrows and vesicles denote the protein trafficking, which directs the proteins that are destined to reach the pyrenocyte. The blue membrane adjacent to the nucleus is the part of the pyrenocyte membrane lacking spectrin, glycophorin A, actin cytoskeleton, and other reticulocyte-specific proteins that are differentially sorted. The green arrow represents the direction of the force exerted on the pyrenocyte by a bound macrophage while the red arrow indicates the movement of the reticulocyte away from the center by lamellipodia and filopodia.