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

Yaxuan Liang, William S. Eng, David R. Colquhoun, Rhoel R. Dinglasan, David R. Graham, Lara Mahal

Research output: Contribution to journalArticle

Abstract

Exosomes, also known as microvesicles (EMVs), are nanosized 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.

Original languageEnglish (US)
Pages (from-to)32526-32537
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number47
DOIs
StatePublished - Nov 21 2014

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Exosomes
Glycosylation
Polysaccharides
Glycoproteins
Protein Transport
Sorting
Cell signaling
Cell Physiological Phenomena
Proteins
Cell membranes
Nanoparticles
Virulence
Tumors
Chemical activation
Cells
Cell Membrane
Pharmacology
Chemical analysis
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment. / Liang, Yaxuan; Eng, William S.; Colquhoun, David R.; Dinglasan, Rhoel R.; Graham, David R.; Mahal, Lara.

In: Journal of Biological Chemistry, Vol. 289, No. 47, 21.11.2014, p. 32526-32537.

Research output: Contribution to journalArticle

Liang, Yaxuan ; Eng, William S. ; Colquhoun, David R. ; Dinglasan, Rhoel R. ; Graham, David R. ; Mahal, Lara. / Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 47. pp. 32526-32537.
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