Network organization of the human exosomes

Exosomes, nano-sized bilayered proteolipids, play multiple roles in intercellular communication. Although many exosomal proteins have been identified, their functional interrelationships and the mechanisms of exosome biogenesis remain unknown. By interrogating proteomic data using systems approaches, we have created a human exosome network, which comprises 1491 interactions between 957 exosomal proteins. Moreover, physically and functionally interconnected protein complexes form functional modules involved in exosome biogenesis and functions. Specifically, we discovered that SRC signaling plays a major role in exosome biogenesis, and confirmed that inhibition of SRC kinase decreased the intracellular biogenesis and cell surface release of exosomes. Our study provides global insights into the cargo-sorting, biogenesis, and pathophysiological roles of these complex extracellular organelles.