Cells regulate their interaction with the environment via cell surface expression of receptors and ligands. Internalization of receptors can induce down-regulation or sequestration. Membrane traffic during export can influence processing of an expressed receptor. Our research focuses on cellular mechanisms of directing and regulating intracellular membrane traffic. In particular we are analyzing the molecular determinants of clathrin-coated vesicle formation at the structural level and in response to receptor signalling. These vesicles are major players in selective update and targeting of membrane proteins during intracellular protein sorting.
A second project in the laboratory investigates the role of intracellular membrane traffic in the assembly and expression of molecules of the major histocompatiblity complex (MHC). These MHC molecules display peptides on the cell surface to alert T cells to the presence of pathogens and are the initiators of both cell-mediated and antibody-mediated immune responses. The display of peptides by MHC molecules is a function of their intracellular transport pathways. We are currently investigating how intracellular pathogens subvert the pathways by which MHC molecules acquire peptides for stimulation of the immune response.
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Liu, SH, Marks, MS and Brodsky, F.M. A dominant negative clathrin mutant differentially affects trafficking of molecules with distinct sorting motifs in the class II MHC pathway. J. Cell Biol. 140, 1023-1037.