To elucidate calnexin functions we have been studying its interaction with a model protein that passes transiently through the ER on its way to the cell surface, the class I histocompatibility molecule. Using various in vivo systems that allow us to interfere with calnexin action, we have been able to show that calnexin facilitates the folding and subunit assembly of class I molecules. I molecules that are unable to assemble. Thus, calnexin functions not only as a molecular chaperone but also as a component of the ER quality control system. Very recently we found that calnexin recognizes nascent proteins in a remarkably novel way.
Current work is focused on three general areas.
Establishing a role for calnexin and other ER chaperones in the retention of mutant proteins associated with human disease. For example, in cystic fibrosis, mutant CFTR molecules remain functional but are prevented from reaching the cell surface. Calnexin as well as other proteins are involved in this immunologically important process. We are examining the role of these proteins by preventing their interactions through mutagenesis and by reconstituting their functions in a heterologous Drosophila expression system. Functional relationship between calreticulin, calnexin, and the ER luminal domain of calnexin.