From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals.

Martina Moras,Sophie D Lefevre,Mariano A Ostuni

doi:10.3389/fphys.2017.01076

Abstract

Erythropoiesis occurs mostly in bone marrow and ends in blood stream. Mature red blood cells are generated from multipotent hematopoietic stem cells, through a complex maturation process involving several morphological changes to produce a highly functional specialized cells. In mammals, terminal steps involved expulsion of the nucleus from erythroblasts that leads to the formation of reticulocytes. In order to produce mature biconcave red blood cells, organelles and ribosomes are selectively eliminated from reticulocytes as well as the plasma membrane undergoes remodeling. The mechanisms involved in these last maturation steps are still under investigation. Enucleation involves dramatic chromatin condensation and establishment of the nuclear polarity, which is driven by a rearrangement of actin cytoskeleton and the clathrin-dependent generation of vacuoles at the nuclear-cytoplasmic junction. This process is favored by interaction between the erythroblasts and macrophages at the erythroblastic island. Mitochondria are eliminated by mitophagy. This is a macroautophagy pathway consisting in the engulfment of mitochondria into a double-membrane structure called autophagosome before degradation. Several mice knock-out models were developed to identify mitophagy-involved proteins during erythropoiesis, but whole mechanisms are not completely determined. Less is known concerning the clearance of other organelles, such as smooth and rough ER, Golgi apparatus and ribosomes. Understanding the modulators of organelles clearance in erythropoiesis may elucidate the pathogenesis of different dyserythropoietic diseases such as myelodysplastic syndrome, leukemia and anemia.

Highlights

Mature red blood cells (RBCs) result from a finely regulated process called erythropoiesis that produces 2 million RBCs every second in healthy human adults (Palis, 2014)
Maturation from erythroid-committed precursors is called terminal erythropoiesis and occurs in the bone marrow (BM) within erythroblastic islands, which consist of a central macrophage surrounded by erythroblasts, and ends in the blood stream where reticulocytes complete their maturation within 1–2 days
While extensive literature is done concerning the general mechanisms of erythropoiesis (Palis, 2014), this review focuses on the mechanisms and molecular actors involved during organelle clearance and membrane remodeling in order to produce fully functional biconcave mature RBCs

Summary

Introduction

Mature red blood cells (RBCs) result from a finely regulated process called erythropoiesis that produces 2 million RBCs every second in healthy human adults (Palis, 2014). The reticulocyte maturation continues, losing 20–30% of the cell surface (Waugh et al, 1997; Da Costa et al, 2001) and eliminating any remaining membrane-bound cytosolic organelles through an autophagy/exosome-combined pathway (Blanc et al, 2005).

Results

Conclusion