The trafficking of macromolecules between different compartments is an essential process in all eukaryotic cells and is used to maintain cellular integrity, to interact with the extracellular environment, and to generally modulate various cellular activities. Numerous advances have been made in understanding different pathways of membrane trafficking and in elucidating some of the factors that regulate them; these advances have demonstrated a striking conservation of these pathways among all eukaryotic cells.
We are studying membrane trafficking using primarily the nematode Caenorhabditis elegans as a model system. We are also using mouse macrophages as a parallel system that complements the genetic studies we carry out in C. elegans. Current projects in the laboratory are:
1) The analysis of endocytosis. We have identified several novel regulators that are required for endocytosis by specialized scavenger cells called coelomocytes in C. elegans.
2) The analysis of lysosomal transport, focusing on CUP-5 in C. elegans and its mammalian ortholog mucolipin-1. Mutations in MCOLN1, the gene that encodes mucolipin-1, results in the lysosome storage disorder Mucolipidosis type IV.
3) The analysis of suppressors of cup-5 mutant defects. We identified several suppressors of cup-5 mutant defects. The analysis of these suppressors will identify the molecular events that exacerbate cup-5 mutant phenotypes. These suppressors also constitute leads towards identifying treatments for Mucolipidosis type IV.
4) The characterization of a novel quality control pathway that is used for the recognition and degradation of misfolded integral membrane proteins at the plasma membrane.