Alexander Sorkin, PhD

  • Professor and Chairman, Cell Biology and Physiology




Education & Training

PhD, Academy of Sciences of the U.S.S.R. (1986)

Campus Address

S368 Biomedical Science Tower South

One-Line Research Description

Cell and molecular biology of dopamine transporter

Dopamine (DA) plays an important role in brain reward, both to natural reinforcers and addictive drugs. Removal of DA from the extracellular space and its transport back into DA neurons is an important mechanism controlling DA neurotransmission. This removal occurs via the DAT. DAT plays important roles in psychomotor stimuÂlant behavÂioral activation and reward. By understanding how DAT activity is regulated, we will better appreÂciÂate its contribution to normal neurotransmission and to brain diseases like drug addicÂtion. Our current research is aimed at characterization of the mechanisms of endocytosis and intracellular trafficking of DAT. One set of projects involves structure-function studies of heterologously-expressed human DAT. We have performed extensive analysis of the molecular mechanisms of DAT endocytosis induced by PKC activation and identified key players involved. Our immediate goal is to elucidate the molecular mechanisms of PKC-dependent endocytosis and also elucidate the mechanisms that control constitutive PKC-independent endocytosis. The main focus in the nest several years will be on the development of in vitro and in vivo experimental models to study trafficking of endogenous DAT in dopaminergic neurons. To this end, we are working in two independent tracks. First, we are developing and characterizing midbrain-striatal organotypic cultures prepared from post-natal rats, and developing the reagents that can be used to manipulate DAT trafficking in these cultures. In the same time, we have generated the knock-in mice with epitope-tagged DAT that should allow quantitative analysis of DAT trafficking in vitro and in vivo in neurons obtained from these mice. Finally, the data obtained using mechanistic analyses will be further developed in experiments with the intact animals to analyze how changes in DAT trafficking at the synapse correlate with the behavior patterns and response of the drugs of abuse.

Representative Publications

Sorkina, T., Ma, S., Larsen, M. B., Watkins, S. C., and Sorkin A. Small molecule induced oligomerization, clustering and clathrin-independent endocytosis of the dopamine transporter (2018) eLife.


Ma, S. and Sorkin, A. (2018). Striatal Synaptosomes Preparation from Mouse Brain. Bio-protocol Bio101: e2996. DOI: 10.21769/BioProtoc.2996.


Cheng, M. H., Guthrie, D.A., Newman, A. H., Bahar, I., and Sorkin, A. Targeting of dopamine transporter to filopodia requires an outward-facing conformation of the transporter. (2017) Sci. Reports 7(1):5399. doi: 10.1038/s41598-017-05637-x.


Caltagarone, J., Ma, S. Sorkin, A. (2015) Dopamine transporter is enriched in filopodia and induces filopodia formation. Mol. Cell. Neuroscience. 2015 Apr 30;68:120-130. PMID: 25936602 


Tomas, A., Vaughan, S. O., Burgoyne, T., Sorkin, A., Hartley., Hochhauser, J. A. D., Futter, C. E. WASH and Tsg101/Alix-dependent diversion of stress-activated EGFR from the canonical endocytic pathway. Nat. Comm. 2015 Jun12;6:7324. PMID: 26066081. 


Cheng, M.H., Hu, F., Block, E., Cobanoglu, MC., Sorkin, A., Bahar, I. Insights into modulation of dopamine transporter function modulation by amphetamine, orphenadrine and cocaine binding. Frontiers Neuropharm. 2015 Jun 9:6:134. PMID: 26106364 


Fortian, A., Dionne, L. K., Hong, S. H., Kim, W., Gygi, S. P., Watkins, S., Sorkin, A. (2015) Endocytosis of ubiquitylation-deficient EGF receptor mutants via clathrin coated pits is mediated by ubiquitylation. Traffic. 2015 11: 1137-1154 


Block, E., Nuttle, J., Balcita-Pedicino, J. J., Caltagarone, J., Watkins S. C., Sesack, S. R., Sorkin, A. (2015) Brain region-specific trafficking of the dopamine transporter. J. Neurosci. (2015). 35(37):12845- 58. PMID: 26377471 


Martínez-Mármo, R., Comes, N., Pérez-Verdaguer, M., Vicente, R., Pujadas, L., Soriano, E., Sorkin, A., Felipe, A. (2015) Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis. Cell.Mol.Life Sci. In press. 


Pinilla-Macua I, Watkins, S. C., and Sorkin, A. (2016) Endocytosis separates active EGF receptors from endogenously labeled HRas and diminishes signaling to MAP kinases from endosomes. Proc. Natl. Acad. Sci. USA. In press. 


Vina-Vilaseca, A., and Sorkin, A. ÂLysine63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes. J. Biol. Chem. 285, 7645-56, 2010.


Zahniser, N. R., and Sorkin, A. Trafficking of Dopamine Transporters in Psychostimulant Actions. Sem. Cell Dev. Biol. 20, 411-417, 2009.


Sorkina, T., Richards, T. L., Rao, A., Zahniser, N. R., and Sorkin, A. Negative Regulation of Dopamine Transporter Endocytosis by Membrane-Proximal N-Terminal Residues. J. Neuroscience. 9, 1361_1374, 2009.


Miranda, M., Dionne, K. R., Sorkina, T., and Sorkin, A. Three ubiquitin conjugation sites in the amino-terminus of the dopamine transporter mediate protein kinase C dependent endocytosis of the transporter. Mol. Biol. Cell. 18, 313-323, 2007.


Sorkina, T., Miranda, M., Dionne, K. R., Hoover, B.R., Zahniser N.R., and Sorkin, A. RNA Interference Screen Reveals an Essential Role of Nedd4_2 in Dopamine Transporter Ubiquitination and Endocytosis. J. Neuroscience. 26, 8195_ 8205, 2006.