The sorting of proteins to individual subcellular compartments is crucial for the proper segregation of biochemical functions in all eukaryotic cells. Because peroxisomes do not contain DNA, all the peroxisomal matrix and membrane proteins must be encoded by nuclear genes whose products are then imported post-translationally into the organelle. Following our discovery of a consensus tripeptide that serves as the peroxisomal targeting signal (PTS) and its remarkable conservation in many peroxisomal proteins, we plan to use biochemical, immunological and genetic approaches to identify the proteins that play a role in peroxisomal targeting. We also wish to understand the mechanism of translocation of proteins across the peroxisomal membrane.
The aims of the proposal are: (1) To identify the targeting signal in a peroxisomal membrane protein. (2) To analyze the import of proteins containing functional and non- functional PTSs into peroxisomes in vitro. (3) To identify, isolate and characterize the PTS receptor by biochemical and immunological methods. (4) To investigate the mechanism of import and the directionality of proteins transport across the peroxisomal membrane. (5) To isolate and characterize yeast mutants deficient in peroxisomal targeting. The conservation and the simplicity of the PTS suggest that the translocation of proteins into the peroxisomes should serve as an excellent model for the transport of proteins across membranes in general. An understanding of peroxisomal targeting of proteins should also shed light on the mechanisms of protein sorting in cells, and may help in the design of rational therapies for Zellweger syndrome patients who appear to be deficient in the import of proteins into the organelle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK041737-01A1
Application #
3242592
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1990-05-10
Project End
1995-04-30
Budget Start
1990-05-10
Budget End
1991-04-30
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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