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Exosome biogenesis and retrovirus budding
Animal cells secrete small vesicles (~50-250 nm diameter) that have the same topology as the cell. These vesicles, known as exosomes and microvesicles (EMVs), can be taken up by neighboring cells, completing a pathway of intercellular vesicle traffic. Our laboratory studies the molecular mechanisms of EMV biogenesis and uptake, and their contributions to cell polarity, cell:cell interactions, and intercellular signaling. Furthermore, we study the ways in which HIV and other retroviruses use the exosome biogenesis pathway for the formation of infectious virions, and the consequences of their EMV origin. Currently, we are investigating the following questions: What are the cis-acting signals that target proteins to secreted vesicles? What are the trans-acting factors that mediate EMV biogenesis? What are the mechanisms of EMV biogenesis? How does HIV exploit the EMV biogenesis pathway? How do infection-boosting, protease-generated ligands promote HIV infectivity?
Gan X, Gould SJ. (2012) HIV Pol Inhibits HIV Budding and Mediates the Severe Budding Defect of Gag-Pol. PLoS One. 7:e29421
Gan X and Gould SJ. (2011) Identification of an inhibitory budding signal that blocks the release of HIV particles and exosome/microvesicle proteins. Mol. Biol. Cell. 22:817-830
Shen B, Wu N, Yang JM, and Gould SJ. (2011) Protein targeting to exosomes/microvesicles by plasma membrane anchors. J. Biol. Chem. 286:14383-14395
Shen B, Fang Y, Wu N and Gould,SJ. (2011) Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway. J. Biol. Chem. 286:44162-76