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¹ Department of Biological Chemistry and ² Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Correspondence to Stephen J. Gould: sgould{at}jhmi.edu

Exosomes are secreted, single membrane organelles of 100 nm diameter. Their biogenesis is typically thought to occur in a two-step process involving (1) outward vesicle budding at limiting membranes of endosomes (outward = away from the cytoplasm), which generates intralumenal vesicles, followed by (2) endosome–plasma membrane fusion, which releases these internal vesicles into the extracellular milieu as exosomes. In this study, we present evidence that certain cells, including Jurkat T cells, possess discrete domains of plasma membrane that are enriched for exosomal and endosomal proteins, retain the endosomal property of outward vesicle budding, and serve as sites of immediate exosome biogenesis. It has been hypothesized that retroviruses utilize the exosome biogenesis pathway for the formation of infectious particles. In support of this, we find that Jurkat T cells direct the key budding factor of HIV, HIV Gag, to these endosome-like domains of plasma membrane and secrete HIV Gag from the cell in exosomes.

A.M. Booth and Y. Fang contributed equally to this article.

Abbreviations used in this paper: MVB, multivesicular body; MVE, multivesicular endosome; PE, phosphatidyl ethanolamine; VPS, vacuolar protein sorting.

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