Abstract

The peroxisome biogenesis disorders (PBD) occur in approximately 1/25,000 live births and result from the loss of multiple peroxisomal metabolic activities. However, unlike most other metabolic diseases, the genes defective in the PBD do not encode the enzymes involved in these metabolic functions. Rather the PBD are caused by defects in peroxins, proteins that are involved in assembling the peroxisome. Dr. Gould proposes to continue investigation into the mechanism of peroxisome biogenesis in both yeast and human cell systems, maximizing the advantages of each. This research has already led to the identification and preliminary characterization of several novel peroxins. Also, the performance of this work at a pre-eminent center for the study of the PBD, together with the synergy derived from analysis of the process in both yeast and human cell systems, has led to the identification of 4 new genes responsible for the PBD. It is anticipated the aims of this proposal will further elucidate mechanisms of peroxisome biogenesis and how they are disrupted in the PBD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK045787-09S1
Application #
6500840
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Haft, Carol R
Project Start
1993-08-01
Project End
2002-03-31
Budget Start
2000-08-01
Budget End
2002-03-31
Support Year
9
Fiscal Year
2001
Total Cost
$81,750
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

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

Showing the most recent 10 out of 44 publications