Member, Institute of Molecular Biology
Stevens: Institute of Molecular Biology Webpage

B.A., San Francisco State University, 1974. Ph.D., California Institute of Technology, 1980 (Sunney Chan). Postdoctoral: University of California, Berkeley, 1980–83 (Randy Schekman). Honors and Awards: Damon Runyon-Walter Winchell Postdoctoral Fellow, 1980–82; American Cancer Society Faculty Research Award, 1988–93; Medical Research Foundation of Oregon Discovery Award, 1997; Elected Fellow, American Academy of Microbiology, 1998; College of Arts and Sciences Distinguished Professor, 2005. At Oregon since 1983.

Research Interests

Stevens’ research group is concerned with the process of protein sorting and membrane assembly in yeast cells. Using yeast molecular genetics, we have identified a large number of genes required for the correct targeting and transport of proteins to the membrane-bounded organelle called the vacuole. These vacuolar protein sorting (VPS) genes have been found to encode proteins such as a dynamin-like GTPase, a protein-sorting receptor, a protein kinase, a lipid kinase, a RAS inhibitor-like protein, and an increasingly large number of proteins involved in transport vesicle targeting/fusion such as Rab-like GTPases and SNARE proteins. To characterize the function of some of these proteins we use biochemical, cell biological and molecular genetic approaches. Biochemical approaches are being used to isolate a number of the VPS proteins and to study the membrane-associated protein complexes in which they are found. We use mass spectrometry to identify the unknown proteins present in these sorting complexes.

The group also has a long-standing interest in the assembly, targeting, structure and function of the vacuolar H+-translocating ATPase (V-ATPase; see figure). The V-ATPase complex consists of fourteen subunits, and all but one of these are encoded by a single yeast gene. The large hydrophobic “a” subunit has two isoforms, Vph1 and Stv1, with the Vph1-associated V-ATPase complex localizing to the vacuole membrane and the Stv1-associated V-ATPase restricted to Golgi and endosomal membranes. The mechanism of differential localization of these two forms of the yeast V-ATPase is under active investigation in the lab. We are investigating the proteins responsible for maintaining this differential localization, as well as the protein-based signals that specify the distinct localizations.

We have also identified four genes that encode proteins required for V-ATPase complex assembly but are not themselves part of the final V-ATPase enzyme complex. These four proteins reside in the yeast cell endoplasmic reticulum and constitute the dedicated assembly machinery for the V-ATPase. A number of molecular genetic and biochemical approaches are being taken to characterize the assembly complex and to study the interaction of this assembly complex with V-ATPase subunits along the assembly pathway within the endoplasmic reticulum.

 

Selected Publications:

Bowers, K. and T.H. Stevens. Protein transport from the late Golgi to the vacuole in the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta, 1744, 438-454 (2005).

Malkus, P., Graham, L.A., Stevens, T.H. and R. Schekman. Role of Vma21p in assembly and transport of the yeast vacuolar ATPase. Mol. Biol. Cell, 15, 5075-5091 (2004).

Flannery, A.R., Graham, L.A. and T.H. Stevens. Topological characterization of the c, c', and c'' subunits of the Vacuolar ATPase from the yeast Saccharomyces cerevisiae. J. Biol. Chem., 279, 39856-39862 (2004).

Bowers, K., Lottridge, J., Helliwell, S.B., Goldthwaite, L.M., Luzio, J.P. and T.H. Stevens. Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic, 5, 194-210 (2004).

Graham, L.A., Flannery, A.R. and T.H. Stevens. Structure and assembly of the yeast V-ATPase. J. Bioenerg. Biomembr., 35, 301-312 (2003).

Conibear, E., Cleck, J.N. and T.H. Stevens. Vps51p mediates the association of the GARP (Vps52/53/54) complex with the Golgi t-SNARE Tlg1p. Mol. Biol. Cell, 14, 1610-1623 (2003).

Additional Publications

To Contact Dr. Stevens:
Phone: 541-346-5884
stevens@molbio.uoregon.edu

WEBMASTER
lynde@uoregon.edu