Journal
JOURNAL OF PROTEOME RESEARCH
Volume 11, Issue 2, Pages 1144-1151Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr200842h
Keywords
exosomes; microvesicles; ectosomes; network biology; proteome; SRC signaling
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Funding
- NRF
- MEST [2009-0080709, 20100-017496]
- Korea Science and Engineering Foundation (KOSEF) NCRC
- Korea government (MEST) [2010-0028447]
- National Research Foundation of Korea [2009-0080709] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Various mammalian cells including tumor cells secrete extracellular vesicles (EVs), otherwise known as exosomes and microvesicles. EVs are nanosized bilayered proteolipids and play multiple roles in intercellular communication. Although many vesicular proteins have been identified, their functional interrelationships and the mechanisms of EV biogenesis remain unknown. By interrogating proteomic data using systems approaches, we have created a protein interaction network of human colorectal cancer cell-derived EVs which comprises 1491 interactions between 957 vesicular proteins. We discovered that EVs have well-connected clusters with several hub proteins similar to other subcellular networks. We also experimentally validated that direct protein interactions between cellular proteins may be involved in protein sorting during EV formation. Moreover, physically and functionally interconnected protein complexes form functional modules involved in EV biogenesis and functions. Specifically, we discovered that SRC signaling plays a major role in EV biogenesis, and confirmed that inhibition of SRC kinase decreased the intracellular biogenesis and cell surface release of EVs. Our study provides global insights into the cargo-sorting, biogenesis, and pathophysiological roles of these complex extracellular organelles.
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