PROTEIN IMPORT AND DEGRADATION IN THE YEAST VACUOLE

Project: Research project

Project Details

Description

A novel pathway of protein targeting into the yeast vacuole for
degradation has been identified in Saccharomyces cerevisiae.
Fructose-1,6-bisphosphatase (FBPase), an important enzyme in the
gluconeogenesis pathway, is imported from the cytosol to the vacuole for
degradation when cells are transferred to media containing fresh glucose.
Targeting and degradation of FBPase requires ubiquitin conjugation,
endosomal formation, and peroxisomal assembly. Peroxisomes are important for the oxidation of fatty acids, alcohols, and
amines in all organisms. Patients lacking peroxisomes (Zellweger's
syndrome) display many abnormalities with a result of death within a few
years after birth. In Saccharomyces cerevisiae, peroxisomes are
delivered to the vacuole for degradation in response to glucose.
Internalization of peroxisomes by the vacuole appears to participate in
FBPase degradation since mutants lacking recognizable peroxisomes are
defective in glucoseinduced degradation of FBPase. The findings that
both FBPase and peroxisomes are targeted to the vacuole for degradation
in response to glucose indicate that vacuolar protein degradation plays
an important role in regulating cellular metabolism. To understand the pathway of vacuolar protein degradation at the
molecular and the cellular level, we propose to: (1) study the role of
peroxisomes in promoting the import and degradation of FBPase by cell
fractionation and immunoelectron microscopy; (2) identify a putative
receptor that mediates the import process by crosslinking and
immunoprecipitation; (3) examine the importance of endosomal formation
in FBPase degradation; (4) reconstitute an in vitro system to test
directly the role of organelle assembly and ubiquitin conjugation in the
import process.
StatusFinished
Effective start/end date5/1/934/30/96

Funding

  • National Institutes of Health: $241,328.00

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