Scientists at the Montreal Neurological Institute and the Montreal Proteomics Network at McGill University have published the most complete picture to date of the components of the molecular machinery that controls the entry of nutrients and other molecules into cells. In a study published in the Proceedings of the National Academy of Sciences of the USA (PNAS), Dr. Peter McPherson and colleagues used proteomics, the large-scale study of proteins, to identify the protein complement of clathrin-coated vesicles. These vesicles are the vehicles by which cells are able to take up nutrients, such as cholesterol, from their environment. Defects in this uptake process have profound repercussions on cellular function and human health. For example, genetic diseases that lead to deficiencies in cholesterol uptake cause elevations in plasma cholesterol levels and early-onset coronary atherosclerosis. In the brain, problems in the uptake process involving clathrin-coated vesicles can disrupt the transmission of signals between nerve cells. This can lead to a number of disorders including defects in the ability to form new memories.
“Proteins are the workhorses in our cells,” explained Dr. McPherson, Associate Professor of Neurology and Neurosurgery, and Anatomy and Cell Biology at the Montreal Neurological Institute (MNI) at McGill University. “Increasingly, we are learning that proteins don’t work in isolation, but function in large arrays that form protein machines. Proteomics is exciting because it allows us to breakdown this complex machine into its component parts. We can then figure out how it is assembled, how the proteins interact with one another, and what goes wrong in disease.
“The study from Dr. McPherson and his colleagues is fundamental to our understanding of the cellular uptake process because it provides a comprehensive molecular inventory of the clathrin-coated vesicle. Its results have broad implications for a variety of fields in biology and medicine,” said Dr. Pietro De Camilli, Professor of Cell Biology, Yale University School of Medicine and Investigator, Howard Hughes Medical Institute.
Sandra McPherson | McGill University
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