Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane.
Exosomes are secreted, single membrane organelles of approximately 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.
Booth
Amy M
AM
Department of Biological Chemistry and 2Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Fang
Yi
Y
Fallon
Jonathan K
JK
Yang
Jr-Ming
JM
Hildreth
James E K
JE
Gould
Stephen J
SJ
D015703:Antigens, CD / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D015683:Gene Products, gag / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D019169:Jurkat Cells; D008563:Membrane Lipids / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure; D014779:Virus Replication / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; C554586:CD63 protein, human; C554798:CD81 protein, human; D015683:Gene Products, gag; D008563:Membrane Lipids; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D054301:gag Gene Products, Human Immunodeficiency Virus; C109809:p2 gag peptide, Human immunodeficiency virus 1