The long-term objective of the proposal is to elucidate the mechanisms of exosome biogenesis and to explore the scope and limitation of the relationship between exosomes and retroviruses. Exosomes are small, secreted organelles with the same topology and similar size as retrovirus particles and it has been proposed that retroviruses such as HIV are "Trojan exosomes". Recent studies provide support for this hypothesis and warrant more detailed studies of how exosomes are made. Using a wide variety of animal cell culture systems and molecular genetic and biochemical techniques we will (aim 1) determine the scope and limitation of the relationship between exosomes and retroviruses such as HIV, (aim 2) identify the signals that target exosomal proteins to sites of exosome budding and into exosomes, (aim 3) identify and characterize the genes and proteins that mediate exosome biogenesis, and (aim 4) explore the additional roles of exosome biogenesis pathways in the cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045787-19
Application #
8027735
Study Section
Cell Structure and Function (CSF)
Program Officer
Haft, Carol R
Project Start
1993-08-01
Project End
2013-02-28
Budget Start
2011-03-01
Budget End
2013-02-28
Support Year
19
Fiscal Year
2011
Total Cost
$437,501
Indirect Cost
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Yang, Jr-Ming; Gould, Stephen J (2013) The cis-acting signals that target proteins to exosomes and microvesicles. Biochem Soc Trans 41:277-82
Gan, Xin; Gould, Stephen J (2012) HIV Pol inhibits HIV budding and mediates the severe budding defect of Gag-Pol. PLoS One 7:e29421
Shen, Beiyi; Wu, Ning; Yang, Jr-Ming et al. (2011) Protein targeting to exosomes/microvesicles by plasma membrane anchors. J Biol Chem 286:14383-95
Shen, Beiyi; Fang, Yi; Wu, Ning et al. (2011) Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway. J Biol Chem 286:44162-76
Gan, Xin; Gould, Stephen J (2011) Identification of an inhibitory budding signal that blocks the release of HIV particles and exosome/microvesicle proteins. Mol Biol Cell 22:817-30
Fang, Yi; Wu, Ning; Gan, Xin et al. (2007) Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 5:e158
Booth, Amy M; Fang, Yi; Fallon, Jonathan K et al. (2006) Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol 172:923-35
Erdmann, Ralf; Gould, Stephen J (2002) Visualization and purification of yeast peroxisomes. Methods Enzymol 351:365-81
Harper, Courtney C; South, Sarah T; McCaffery, J Michael et al. (2002) Peroxisomal membrane protein import does not require Pex17p. J Biol Chem 277:16498-504
Jones, J M; Morrell, J C; Gould, S J (2001) Multiple distinct targeting signals in integral peroxisomal membrane proteins. J Cell Biol 153:1141-50

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