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

Rebecca E. Griffiths, Sabine Kupzig, Nicola Cogan, Tosti J. Mankelow, Virginie M. S. Betin, Kongtana Trakarnsanga, Edwin J. Massey, Jon D. Lane, Stephen F. Parsons, David J. Anstee

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80 Citations (Scopus)

Abstract

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 beta 1 integrin) through the endosome-exosome pathway. In contrast, late maturation is characterized by the generation of large glycophorin A-decorated vesicles of autophagic origin. (Blood. 2012;119(26):6296-6306)

Original languageEnglish
Pages (from-to)6296-6306
Number of pages11
JournalBlood
Volume119
Issue number26
DOIs
Publication statusPublished - 28 Jun 2012

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Griffiths, R. E., Kupzig, S., Cogan, N., Mankelow, T. J., Betin, V. M. S., Trakarnsanga, K., Massey, E. J., Lane, J. D., Parsons, S. F., & Anstee, D. J. (2012). Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis. Blood, 119(26), 6296-6306. https://doi.org/10.1182/blood-2011-09-376475