Maturing reticulocytes internalize plasma membrane in glycophorin A–containing vesicles that fuse with autophagosomes before exocytosis

The erythrocyte is one of the best characterized human cells. However, studies of the process whereby human reticulocytes mature to erythrocytes have been hampered by the difficulty of obtaining sufficient numbers of cells for analysis. In the present study, we describe an in vitro culture system pr...

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Bibliographic Details
Published in:Blood 2012-06, Vol.119 (26), p.6296-6306
Main Authors: Griffiths, Rebecca E., Kupzig, Sabine, Cogan, Nicola, Mankelow, Tosti J., Betin, Virginie M.S., Trakarnsanga, Kongtana, Massey, Edwin J., Lane, Jon D., Parsons, Stephen F., Anstee, David J.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Cell Differentiation
Cell Membrane - metabolism
Erythrocytes - physiology
Erythrocytes - ultrastructure
Exocytosis - physiology
Glycophorins - metabolism
Hematologic and hematopoietic diseases
Humans
Medical sciences
Membrane Fusion - physiology
Microscopy, Confocal
Oxygen - metabolism
Phagosomes - metabolism
Phagosomes - physiology
Red Cells, Iron, and Erythropoiesis
Reticulocytes - metabolism
Reticulocytes - physiology
Reticulocytes - ultrastructure
Transport Vesicles - metabolism
Transport Vesicles - physiology
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Summary:The erythrocyte is one of the best characterized human cells. However, studies of the process whereby human reticulocytes mature to erythrocytes have been hampered by the difficulty of obtaining sufficient numbers of cells for analysis. In the present study, we describe an in vitro culture system producing milliliter quantities of functional mature human adult reticulocytes from peripheral blood CD34+ cells. We show that the final stage of reticulocyte maturation occurs by a previously undescribed mechanism in which large glycophorin A–containing vesicles forming at the cytosolic face of the plasma membrane are internalized and fuse with autophagosomes before expulsion of the autophagosomal contents by exocytosis. Early reticulocyte maturation is characterized by the selective elimination of unwanted plasma membrane proteins (CD71, CD98, and β1 integrin) through the endosome-exosome pathway. In contrast, late maturation is characterized by the generation of large glycophorin A–decorated vesicles of autophagic origin.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2011-09-376475