Prof. Gergely LUKACS
Department of Physiology – McGill University (Montreal, Canada)
Molecular players and mechanisms of plasma membrane proteostasis in health and diseases ; cystic fibrosis and beyond.
Preserving the function of the plasma membrane proteome is pivotal for cellular and organism physiology to coordinate cell-cell communications, development, differentiation, signaling, metabolism and transport. Using the cystic fibrosis transmembrane conductance regulator (CFTR) variants and other model proteins, we queried the molecular and cellular basis of two fundamental and complementary aspects of the quality control of plasma membrane proteins. Based on the results, we propose a model that incorporates two functionally opposite, but complementary pathways as fate determinants of metastable and non-native plasma membrane proteins; the ubiquitination-dependent lysosomal degradation pathway and the molecular chaperone-mediated refolding route. Highlights of the functional duality of molecular chaperones systems in these process will be discussed, including evidence suggesting the capacity of chaperones to partially suppress mutations imposed conformational perturbations of CFTR at the cell surface and at the single molecule level in vitro.