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J Biol Chem. 2014 Nov 21;289(47):32526-37. doi: 10.1074/jbc.M114.606269. Epub 2014 Sep 26.

Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment.

Author information

1
From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003-6688.
2
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and.
3
W. Harry Feistone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
4
From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003-6688, lkmahal@nyu.edu.

Abstract

Exosomes, also known as microvesicles (EMVs), are nano-sized membranous particles secreted from nearly all mammalian cell types. These nanoparticles play critical roles in many physiological processes including cell-cell signaling, immune activation, and suppression and are associated with disease states such as tumor progression. The biological functions of EMVs are highly dependent on their protein composition, which can dictate pathogenicity. Although some mechanisms have been proposed for the regulation of EMV protein trafficking, little attention has been paid to N-linked glycosylation as a potential sorting signal. Previous work from our laboratory found a conserved glycan signature for EMVs, which differed from that of the parent cell membranes, suggesting a potential role for glycosylation in EMV biogenesis. In this study, we further explore the role of glycosylation in EMV protein trafficking. We identify EMV glycoproteins and demonstrate alteration of their recruitment as a function of their glycosylation status upon pharmacological manipulation. Furthermore, we show that genetic manipulation of the glycosylation levels of a specific EMV glycoprotein, EWI-2, directly impacts its recruitment as a function of N-linked glycan sites. Taken together, our data provide strong evidence that N-linked glycosylation directs glycoprotein sorting into EMVs.

KEYWORDS:

Carbohydrate Function; Exosome; G3BP; Galectin; Glycosylation; IgFS8; Intracellular Trafficking; Membrane Trafficking; Microvesicle; Tetraspanin

PMID:
25261472
PMCID:
PMC4239607
DOI:
10.1074/jbc.M114.606269
[Indexed for MEDLINE]
Free PMC Article

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