Alexander Sorkin, Ph.D.

  • Richard Beatty Mellon Professor and Chair
  • Department of Cell Biology

Education & Training

  • Ph.D. in Cell Biology from Russia Institute of Cytology, Academy of Sciences, Leningrad, Russia, 1986
  • B.S. in Biology, Chemistry from Leningrad State Pedagogical Institute, Leningrad, Russia, 1979

Research Interest Summary

Mechanisms and functional role of endocytic trafficking of epidermal growth factor (EGF) receptor in cancer cells and the dopamine transporter in the brain

Research Categories

Research Interests

The main focus of the research in the laboratory is currently split into two major directions which are apparently distinct from each other with respect to the biological systems involved, their relation to the human disease, and experimental models used. However, the main idea underlying both directions is conceptually the same - to understand how endocytosis and post-endocytic trafficking regulates function(s) of the transmembrane proteins, such as receptors and transporters. In particular, we aim at elucidating the molecular mechanisms of endocytosis of growth factor receptors using a prototypic member of the family, epidermal growth factor (EGF) receptor, and analysis of the role of endocytosis in spatial and temporal regulation of signal transduction by the EGF receptor. In the second direction, we would like to elucidate the role of trafficking processes in the regulation of dopaminergic neurotransmission by the plasma membrane dopamine transporter (DAT). By understanding how DAT activity is regulated, we will better appre­ci­ate its contribution to normal neurotransmission and to brain diseases like drug addic­tion.

Representative Publications

Galperin, E., Verkhusha, V., and Sorkin, A. (2004) Three-fluorochrome FRET to analyze protein interactions in living cells. Nature Methods 1: 209-217. 

Boese, Q., Samarsky, D., Huang, F., and Sorkin, A. (2006) siARRAY reverse transfection format (RTF)TM: A rapid method for RNAi-based high-throughput studies of biological pathways. Nature Methods. Application Notes, 1, an37.

Huang, F., Kirkpatrick, D., Jiang, X., Gygi, S. and Sorkin, A. (2006) Differential Regulation of EGF Receptor Internalization and Degradation by Multi-Ubiquitination within the Kinase Domain. Molecular Cell. 21, 737-748.

Sorkina, T., Miranda, M., Dionne, K. R., Hoover, B.R., Zahniser N.R., and Sorkin, A. (2006) RNA Interference Screen Reveals an Essential Role of Nedd4–2 in Dopamine Transporter Ubiquitination and Endocytosis. J. Neuroscience. 26, 8195– 8205.

Duex, J. E. and Sorkin, A. RNA interference screen identifies Usp18 as a regulator of EGF receptor synthesis (2009) Mol. Biol. Cell 20, 1833–1844.

Sorkin, A., von Zastrow, M. Endocytosis and signaling: intertwining molecular networks. Nat Rev Mol Cell Biol. (2009) Sep; 10(9):609-22. Review.

Goh, L.K., Huang, F., Kim, W., Gygi, S., Sorkin, A. Multiple mechanisms collectively regulate clarthrin-mediated endocytosis of the epidermal growth factor receptor. J. Cell Biol. 2010 May 31; 189(5):871-83.

Huang, F., Zeng, X., Kim, W., Balasubramani, M., Fortian, A., Gygi, S. P., Yates, N. A., and Sorkin, A. Lysine 63-linked polyubiquitination is required for EGF receptor degradation Proc. Natl. Acad. Sci. USA (2013) 110: 15722-7.

Goh, L. K., and Sorkin, A. (2013) Endocytosis of receptor tyrosine kinases. Cold Spring Harb Perspect Biol 2013;5:a017459.

Fortian, A. and Sorkin, A. Live cell fluorescence imaging reveals high stoichiometry of Grb2 binding to the EGF receptor sustained during endocytosis. (2014) J. Cell Sci. 127:432-44. Epub 2013 Nov 20.

Full List of Publications