Survivin: a new player during erythroblast maturation

Abstract

E nucleation of erythroblasts is a phenomenon unique to mammals. During their terminal stage of differentiation, mammalian erythroblasts exit the cell cycle and enucleate. They complete their terminal differentiation and enucleation in "erythroid niches" composed of erythroblastic islands nested in extracellular matrix proteins. [1][2][3][4][5][6] It has been recently reported that, in the very last stage of enucleation, not only proteins but also specialized regions of the lipid bilayer, known as lipid rafts, as well as organelles participate in the extrusion of the nucleus. 7Approximately 120 million reticulocytes are generated each minute in our body. Macrophages phagocyte and recycle a similar number of extruded nuclei and other organelles, such as mitochondria. In addition, wastes in the reticulocyte are digested through autophagy and extruded via exosomes. Keerthivasan and colleagues shed new light on the functional relationship between enucleation and vesicle trafficking by identifying a novel role for the apoptosis inhibitor, survivin. Is enucleation actually a type of cytokinesis ?One popular postulate is that enucleation is a type of asymmetric cytokinesis. [1][2][3][4][5][6] Although "cytokinesis" generally refers to the phenomenon that occurs as the cell divides into two symmetric daughter cells, in the case of erythroblast enucleation, it entails an asymmetric division into a nucleus (pyrenocyte) and a reticulocyte. 5 The occurrence of an asymmetric cytokinesis is supported by the observation of a concentration of actin in the region extending between the extruding nucleus and the nascent reticulocyte, reminiscent of the actomyosin ring observed during cytokinesis. Furthermore, it has been shown that enucleation requires functional actin and Rac GTPases that participate in the formation of the actin ring. In fact, the actomyosin is likely the main player during enucleation 1 as it has been demonstrated that non-muscle myosin IIB plays also an important role in the enucleation of human erythroblasts. 9One controversial theory is that microtubules may also participate in some phases of the enucleation process because in vitro and in vivo studies in rats show that microtubule-depolymerizing agents inhibit nuclear extrusion. Hence investigations so far mainly offer hints as to the players involved in enucleation but do not present any well-delineated molecular mechanism driving the sequence of events leading to successful enucleation. To address this important issue, Keerthivasan and colleagues have comprehensively investigated a model of asymmetric cytokinesis. Based on their and other groups' experimental data, it is shown that widely used inhibitors of cytokinesis, including blebbistatin, hesperadin or nocodazole, have no effect on postmitotic primary murine erythroblasts. Instead, they propose a novel hypothesis based upon earlier electron micrographs that described an accumulation of vesicles in the region extending between the extruding nucleus and the nascent reticulocyte. 10 Characterization of...