NDLI: Ubiquitination as a Mechanism To Transport Soluble Mycobacterial and Eukaryotic Proteins to Exosomes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jackson, Liam Smith, Victoria L. Schorey, Jeffrey S.
Description	Author Affiliation: Smith VL ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556.); Jackson L ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556.); Schorey JS ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556 schorey.1@nd.edu.)
Abstract	Exosomes are extracellular vesicles of endocytic origin that function in intercellular communication. Our previous studies indicate that exosomes released from Mycobacterium tuberculosis-infected macrophages contain soluble mycobacterial proteins. However, it was unclear how these secreted proteins were targeted to exosomes. In this study, we determined that exosome production by the murine macrophage cell line RAW264.7 requires the endosomal sorting complexes required for transport and that trafficking of mycobacterial proteins from phagocytosed bacilli to exosomes was dependent on protein ubiquitination. Moreover, soluble mycobacterial proteins, when added exogenously to RAW264.7 or human HEK293 cells, were endocytosed, ubiquitinated, and released via exosomes. This suggested that endocytosed proteins could be recycled from cells through exosomes. This hypothesis was supported using the tumor-associated protein He4, which, when endocytosed by RAW264.7 or HEK293 cells, was transported to exosomes in a ubiquitin-dependent manner. Our data suggest that ubiquitination is a modification sufficient for trafficking soluble proteins within the phagocytic/endocytic network to exosomes.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Communication Immunology Endocytosis Physiology Exosomes Metabolism Macrophages Proteins Animals Antigens, Bacterial Bacterial Proteins Cell Line Clathrin Dna-binding Proteins Genetics Endosomal Sorting Complexes Required For Transport Hek293 Cells Heat-shock Proteins Microbiology Pathology Mice Mycobacterium Smegmatis Mycobacterium Tuberculosis Phosphoproteins Protein Transport Rna Interference Rna, Small Interfering Transcription Factors Ubiquitin-protein Ligases Ubiquitination Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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