Area of Research

Neural Degeneration and Repair, Roles of protein ubiquitination in synaptic function and neurodegeneration

Specialization

Protein trafficking in Huntington’s disease and other neurological disorders.

RESEARCH THEME

The overriding theme of our research has been to examine the molecular mechanisms of protein trafficking events that may modulate neurodegeneration. The ability of a cell to function properly relies heavily in its ability to traffic proteins to its correct destination. From maintaining proteins at the cell membrane to permit proper signaling, to sequestering and moving proteins away for their ultimate destruction, knowing when and how proteins are selected and targeted is as critical as understanding the function of the proteins themselves. Our studies focus on two forms of protein trafficking, one that mediates elimination of abnormal cellular proteins and a second that regulates the function of normal cellular proteins.  In the former case we seek to understand how protein cargoes that have been implicated in degenerative diseases are selected for degradation by the macroautophagy pathway, as well as to determine how these degradation pathways impact basal neuronal function.  In the latter case, our goal is to identify how the intramembrane localization of plasmalemmal neurotransmitter transporters may impact their function, and in turn contribute towards neurodegenerative processes.  

SELECTED PUBLICATIONS

Cremona, M.L., Matties, H.J.G., Bowton, E., Speed, N., Lute, B.J., Pau, K., Anderson, M.A.,  Sen, N., Doughty, S.E., Rothman, J.E., Galli, A., Javitch, J.A. and Yamamoto, A. (2011) Flotillin-1 is essential for dopamine transporter endocytosis and reverse-transport of dopamine. Nat. Neurosci. 14:469-477.

Yamamoto, A. and Simonsen, A. (2011) The elimination of accumulated and aggregated proteins: A role for aggrephagy in neurodegeneration. Neurobiol. Dis. 43:17-28

Filimonenko, M., Isakson, P., Finley, K.D., Anderson, M., Melia, Jr., Jeong, H., T.J., Bartlett, B.J., Myers, K.M.,  Birkeland, H.C.G., Lamark, T., Krainc, D., Brech, A., Stenmark, H., Simonsen, A. and Yamamoto, A. (2010) The selective macroautophagic degradation of aggregated proteins requires the PI3-P binding protein, Alfy. Molecular Cell 2: 265-279