John J.M. Bergeron

John J. M. Bergeron D. Phil. Professor, Department of Anatomy and Cell Biology , McGill University Associate Member: Department of Medicine Strathcona Medical Building, Room MZ-9 Tel: (514) 398-6351 Fax: (514) 398-5047 john [dot] bergeron [at] mcgill [dot] ca (E-mail)

Research:

1. Signal transduction in the endosomal apparatus.
2. Protein transport in the endoplasmic reticulum.
3. The molecular structure and function of the Golgi apparatus.

Cells must target proteins correctly for their physiological functions to be realized. Three paradigms of targeting are under study.

1. Ligand-mediated receptor internalization of the activated epidermal growth factor (EGF) and insulin receptor from the liver cell surface to the endosomal apparatus has been analyzed by quantitative electron microscope radioautography, immunocytochemistry and preparative and analytical subcellular fractionation. This has led to the identification of the major tyrosine phosphorylated substrate of the EGF receptor in vivo which is the protooncogene product SHC, as well as a novel endosomal proteinase specific for insulin degradation. The latter is thought to regulate the metabolic versus the mitogenic actions of insulin in target cells.
2. The role of membrane phosphoproteins in the exocytic transport of proteins from the endoplasmic reticulum (ER). Molecular cloning has led to the identification of calnexin, the major molecular chaperone for a number of newly synthesized monomeric membrane and soluble secretory glycoproteins. Calnexin is also a constituent of the quality control apparatus of the ER and has been shown to retain mutant membrane and secretory proteins responsible for the diseases of cystic fibrosis and juvenile hereditary emphysema.
3. The molecular anatomy of the Golgi apparatus. Using new methodology to purify Golgi, a complete identification of membrane proteins defining this organelle has been realized by mass spectrometry and molecular cloning. These studies have led to a new model for protein transport through the Golgi.

Selected Publications:

Zapun, A., S.M. Petrescu, P.M. Rudd, R.A. Dwek, D.Y. Thomas, and J.J.M. Bergeron. 1997. Conformation independent binding of monoglycosylated ribonuclease B to calnexin. Cell. 88: 29-38.

Dominguez, M., K. Dejgaard, J. F_llekrug, S. Dahan, A. Fazel, J.P. Paccaud, D.Y. Thomas, J.J.M. Bergeron, and T. Nilsson. 1998. Gp25L/emp24/p24 protein family members of the cis Golgi network bind both COP I and II coatomer. J. Cell Biol. 140: 751-766.

Authier, F., J.S. Mort, A.W. Bell, B.I. Posner, and J.J.M. Bergeron. 1995. Proteolysis of glucagon within hepatic endosomes by membrane-associated cathepsins B and D. J. Biol. Chem. 270: 15798-15807.