Abstract

This proposal examines the very basic cell biological questions of how eukaryotic cells sort proteins within the Golgi body and separate out those proteins destined for the lysosome, and ultimately deliver these proteins to the lysosome. The simple eukaryote yeast will be used as a model system, since the secretory pathway in yeast has been found to be strikingly similar to that observed in higher eukaryotic organisms. Yeast offers the advantage that it is readily amenable to genetic and biochemical analysis. Yeast mutants will be obtained that are defective in the sorting, packaging and transport of glycoproteins to the lysosome-like vacuole. These mutants will be analyzed to determine precisely what step in the vacuole assembly pathway is defective. In conjunction with studying the components of the vacuole assembly pathway, the recognition of sorting signals present on the vacuolar proteins that target their localization will be investigated. These studies should provide molecular information on the nature of eukaryotic protein recognition signals and how these signals control the intracellular localization of proteins. The diseases pseudo Hurler polydystropy and l-cell disease arise because of genetic defects preventing the correct localization of lysosomal enzymes. In addition, defects in the basic process of secretion may be relevant to the disease cystic fibrosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032448-03
Application #
3281292
Study Section
Genetics Study Section (GEN)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Oregon
Department
Type
Graduate Schools
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403

  Publications

Coonrod, Emily M; Graham, Laurie A; Carpp, Lindsay N et al. (2013) Homotypic vacuole fusion in yeast requires organelle acidification and not the V-ATPase membrane domain. Dev Cell 27:462-8
Coonrod, Emily M; Stevens, Tom H (2010) The yeast vps class E mutants: the beginning of the molecular genetic analysis of multivesicular body biogenesis. Mol Biol Cell 21:4057-60
Schluter, Cayetana; Lam, Karen K Y; Brumm, Jochen et al. (2008) Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex. Mol Biol Cell 19:1282-94
Lottridge, Jillian M; Flannery, Andrew R; Vincelli, Jennifer L et al. (2006) Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body. Proc Natl Acad Sci U S A 103:6202-7
Bowers, Katherine; Stevens, Tom H (2005) Protein transport from the late Golgi to the vacuole in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1744:438-54
Bowers, Katherine; Lottridge, Jillian; Helliwell, Stephen B et al. (2004) Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic 5:194-210
Kweon, Youngseok; Rothe, Anca; Conibear, Elizabeth et al. (2003) Ykt6p is a multifunctional yeast R-SNARE that is required for multiple membrane transport pathways to the vacuole. Mol Biol Cell 14:1868-81
Conibear, Elizabeth; Cleck, Jessica N; Stevens, Tom H (2003) Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlg1p. Mol Biol Cell 14:1610-23
Gerrard, S R; Bryant, N J; Stevens, T H (2000) VPS21 controls entry of endocytosed and biosynthetic proteins into the yeast prevacuolar compartment. Mol Biol Cell 11:613-26
Conibear, E; Stevens, T H (2000) Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol Biol Cell 11:305-23

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