The localization of proteins to the lysosome-like vacuole of the yeast, Saccharomyces cerevisiae, Is a complex process. Unique cellular components must recognize vacuolar proteins, sort them away from secretory proteins, package them into transport vesicles and deliver them to the vacuole via a prevacuolar endosomal compartment. The long term goal of our research is to uncover the underlying molecular mechanisms that are involved in this delivery process. Toward this end, we have turned to the large set of yeast mutants that are defective in protein delivery to the vacuole. The gene products affected in these vps mutants are likely part of the trans-acting cellular machinery that is required for sorting of proteins from a late Golgi compartment to the vacuole. The studies described here focus on one event of the vacuolar protein localization system, the vesicle-mediated delivery of vacuolar proteins from the Golgi sorting compartment to the prevacuolar endosome. This transport step involves a large number of proteins that move vacuolar protein receptors bound with cargo from the Golgi to the endosome. The intracellular trafficking of these receptors are a key point at which flux through the vacuolar protein-sorting pathway is regulated. In mammalain cells, the importance of this sorting pathway is exemplified by the serious lysosomal storage diseases (e.g. I-cell disease) as well as other diseases (e.g. osteoporosis and the progression of certain types of cancer) that result from or are correlated with the mislocalization of lysosomal hydrolases. The long-term goal of this research is to understand the underlying mechanisms that are involved in this delivery process using the yeast vacuolar protein sorting pathway as a model system.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055301-08
Application #
6891345
Study Section
Special Emphasis Panel (ZRG1-CDF-4 (02))
Program Officer
Shapiro, Bert I
Project Start
1997-06-01
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
8
Fiscal Year
2005
Total Cost
$266,044
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905