Tel:503-494-7781
Fax:503-494-8393

Membrane biosynthesis and degradation; metabolism and turnover of plasma membrane proteins; Alzheimer's disease.

Membrane proteins, even those that lie within the same membrane compartment of the cell, are degraded at different rates. One of the most rapidly degraded of all membrane proteins is amyloid precursor protein (APP), a protein that is processed under certain conditions to a small 4 kDa protein called beta-amyloid (ßA4). ßA4 participates in ways that are not completely understood in the formation of amyloid placques that accumulate in the brain and contribute to the etiology of Alzheimer's disease.

I am trying to understand the mechanisms of membrane protein degradation, employing APP turnover as a paradigm for rapidly degraded proteins. The main thrust of this lab is currently to identify cellular proteins that interact with APP to control its metabolism. These proteins are of two kinds. A group of proteins associate with APP in the endoplasmic reticulum to help with and ensure its proper folding and maturation. With the help of a folding assay and chemical cross-linking agents, I am attempting to understand the role of specific helper or chaperone proteins in APP maturation. In a separate project I have found that APP associates with several brain proteins in situ to form a 250 kDa complex. I am trying to isolate this complex so that those APP associated proteins and their role in APP function/metabolism can be identified.
 

Recent Publications:

1. Hare, J.F. Protease inhibitors divert amyloid precursor protein to the secretory pathway. Biochem. Biophys. Res. Commun. 281:1298-1303 (2001).

2. Hare, J.F. Photolabeling Acyl Coa Binding Proteins in Microsome Preparations. FEBS Lett. 375: 188-92 (1995).

3. Hare, J.F. and Holacher, A. Solubility in Non-Ionic Detergents Distinguishes Between Slowly and Rapidly Degraded Plasma Membrane Proteins. J. Biol. Chem. 269: 5981-5988 (1994).