null Peter McPherson, PhD
endocytosis • neurons • membrane trafficking • neurogenerative disease • Parkinson's disease
My research focuses on the use of biochemical, molecular, structural and cellular approaches to identify and functionally characterize proteins that function in the formation of clathrin-coated vesicles (CCVs). CCVs are the major vehicles that proteins use to gain access into cells. We are also interested in discovering whether or not the internalized proteins are targeted for destruction or are returned to the surface of the cell and re-used. We have previously used high throughput mass spectrometry to identify the full complement of CCV proteins in brain. Remarkably, a number of proteins identified in my laboratory have been directly linked to neurological diseases including Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis (ALS), and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Indeed, altered membrane trafficking resulting from protein mutation is emerging as a central theme in neurodegenerative diseases. Understanding the cell biological basis of neurological disease is a new focus of the laboratory.
Ritter, B, Murphy, S., Dokainish, H., Girard, M., Gudheti, M.V., Koslov, G., Halin, M., Philie, J., Jorgensen, E.M., Gehring, K., and McPherson, P.S. (2013) NECAP 1 regulates AP-2 interactions to control vesicle size, number and cargo during clathrin-mediated endocytosis PLoS Biology 11:e1001670).
Girard, M., Larivière, R., Parfitt, D.A., Deane, E.C., Gaudet, R., Nossova, N., Blondeau, F., Prenosil, G., Vermeulen, E.G.M., Duchen, M.R., Richter, A., Shoubridge, E.A., Gehring, K., McKinney, R.A., Brais, B., Chapple, J.P. and McPherson, PS. (2012) Mitochondrial dysfunction and Purkinje cell loss in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS). Proc. Natl. Acad. Sci., USA 109: 1661-1666.
Marat, A., Dokainish, H. and McPherson, P.S. (2011) DENN domain proteins: regulators of Rab GTPase J. Biol. Chem. 286: 13791-13800
Allaire, P.D., Marat, A.L., Dall'Armi, C., Di Paolo, G., McPherson, P.S., and Ritter, B. (2010) The connecdenn DENN domain: A GEF for Rab35 mediating cargo-specific exit from early endosomes. Mol. Cell. 37: 370-382
Poupon, V., Girard, M. Legendre-Guillemin, V., Thomas, S., Bourbionniere, L., Philie, J., Bright, N.A. and McPherson, P.S. (2008) Clathrin-light chains function in mannose phosphate receptor trafficking via regulation of actin assembly. Proc. Natl. Acad. Sci., USA, 105:168-173