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

Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis
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DOI:
10.1182/blood-2011-09-376475
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发表时间:
2012-06-28
期刊:
影响因子:
20.3
通讯作者:
Anstee, David J.
Anstee, David J.
中科院分区:
医学1区
文献类型:
--
作者:
Griffiths, Rebecca E.;Kupzig, Sabine;Anstee, David J.

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红细胞是最具特性的人类细胞之一。然而,由于难以获得足够数量的细胞用于分析,对人类网织红细胞成熟过程的研究一直受到阻碍。在本研究中,我们描述了一种从外周血CD34(+)细胞产生毫升功能成熟的成人网织红细胞的体外培养系统。我们证明,网织红细胞成熟的最后阶段是通过一种以前未描述的机制发生的,在这种机制中,在质膜的胞液面上形成的大的含血糖素A的囊泡被内化并与自噬小体融合,然后通过胞吐作用排出自噬内容物。网织红细胞早期成熟的特征是通过内切体-外切体途径选择性地清除不需要的质膜蛋白(CD71、CD98和β1整合素)。相反,晚成熟的特征是产生大的血糖素A修饰的自噬来源的小泡。(血。2012年;119(26):6296-6306)
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)