QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.055095v1 307/2/729    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chi, L. Articles by Reith, M. E. A. Search for Related Content PubMed PubMed Citation Articles by Chi, L. Articles by Reith, M. E. A.

CELLULAR AND MOLECULAR

Substrate-Induced Trafficking of the Dopamine Transporter in Heterologously Expressing Cells and in Rat Striatal Synaptosomal Preparations

Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, Illinois

Dopamine transporter (DAT) trafficking was assessed by functional measurements of dopamine uptake and by biotinylation of surface proteins followed by gel electrophoresis and Western blotting. In human embryonic kidney (HEK)-293 cells expressing human DAT (HEK-hDAT), pretreatment with dopamine (0.1-100 µM) followed by washout caused reductions in subsequent dopamine uptake (reflected in V_max) with effective dopamine concentrations in the 10 to 100 µM range and pretreatment times of 10 to 60 min. Reductions assessed after 60-min pretreatment with 100 µM dopamine corresponded with decreases measured in surface DAT by the noncleavable biotin method, which were caused, at least in part, by enhanced endocytosis as monitored with cleavable biotin. Pretreatment of rat striatal synaptosomes with dopamine (10 and 100 µM) also caused reductions in DAT uptake activity (V_max), and again the underlying mechanism seemed to be a diminished presence of DAT at the surface of synaptosomes as measured by the noncleavable biotin method. The copresence of cocaine during pretreatment with dopamine prevented the down-regulation of surface DAT. The present results show that DAT surface residency can be regulated by substrate acting on it, not only in cells heterologously expressing DAT but also in situ in rat brain tissue.

Address correspondence to: Dr. Maarten E. A. Reith, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Box 1649, Peoria, IL 61656-1649. E-mail: maartenr{at}uic.edu

This article has been cited by other articles:

				Y. Wei, J. M. Williams, C. Dipace, U. Sung, J. A. Javitch, A. Galli, and C. Saunders Dopamine Transporter Activity Mediates Amphetamine-Induced Inhibition of Akt through a Ca2+/Calmodulin-Dependent Kinase II-Dependent Mechanism Mol. Pharmacol., March 1, 2007; 71(3): 835 - 842. [Abstract] [Full Text] [PDF]

				C. Dipace, U. Sung, F. Binda, R. D. Blakely, and A. Galli Amphetamine Induces a Calcium/Calmodulin-Dependent Protein Kinase II-Dependent Reduction in Norepinephrine Transporter Surface Expression Linked to Changes in Syntaxin 1A/Transporter Complexes Mol. Pharmacol., January 1, 2007; 71(1): 230 - 239. [Abstract] [Full Text] [PDF]

				M. Miranda, K. R. Dionne, T. Sorkina, and A. Sorkin Three Ubiquitin Conjugation Sites in the Amino Terminus of the Dopamine Transporter Mediate Protein Kinase C-dependent Endocytosis of the Transporter Mol. Biol. Cell, January 1, 2007; 18(1): 313 - 323. [Abstract] [Full Text] [PDF]

				T. Sorkina, M. Miranda, K. R. Dionne, B. R. Hoover, N. R. Zahniser, and A. Sorkin RNA Interference Screen Reveals an Essential Role of Nedd4-2 in Dopamine Transporter Ubiquitination and Endocytosis J. Neurosci., August 2, 2006; 26(31): 8195 - 8205. [Abstract] [Full Text] [PDF]

				K. M. Kahlig, B. J. Lute, Y. Wei, C. J. Loland, U. Gether, J. A. Javitch, and A. Galli Regulation of Dopamine Transporter Trafficking by Intracellular Amphetamine Mol. Pharmacol., August 1, 2006; 70(2): 542 - 548. [Abstract] [Full Text] [PDF]

				M. A. Cervinski, J. D. Foster, and R. A. Vaughan Psychoactive Substrates Stimulate Dopamine Transporter Phosphorylation and Down-regulation by Cocaine-sensitive and Protein Kinase C-dependent Mechanisms J. Biol. Chem., December 9, 2005; 280(49): 40442 - 40449. [Abstract] [Full Text] [PDF]

				B. G. Garcia, Y. Wei, J. A. Moron, R. Z. Lin, J. A. Javitch, and A. Galli Akt Is Essential for Insulin Modulation of Amphetamine-Induced Human Dopamine Transporter Cell-Surface Redistribution Mol. Pharmacol., July 1, 2005; 68(1): 102 - 109. [Abstract] [Full Text] [PDF]

				L. D. Jayanthi, D. J. Samuvel, R. D. Blakely, and S. Ramamoorthy Evidence for Biphasic Effects of Protein Kinase C on Serotonin Transporter Function, Endocytosis, and Phosphorylation Mol. Pharmacol., June 1, 2005; 67(6): 2077 - 2087. [Abstract] [Full Text] [PDF]

				D. Wang and M. W. Quick Trafficking of the Plasma Membrane {gamma}-Aminobutyric Acid Transporter GAT1: SIZE AND RATES OF AN ACUTELY RECYCLING POOL J. Biol. Chem., May 13, 2005; 280(19): 18703 - 18709. [Abstract] [Full Text] [PDF]

				D. J. Samuvel, L. D. Jayanthi, N. R. Bhat, and S. Ramamoorthy A Role for p38 Mitogen-Activated Protein Kinase in the Regulation of the Serotonin Transporter: Evidence for Distinct Cellular Mechanisms Involved in Transporter Surface Expression J. Neurosci., January 5, 2005; 25(1): 29 - 41. [Abstract] [Full Text] [PDF]

				J. Gates Jr., S. M. Ferguson, R. D. Blakely, and S. Apparsundaram Regulation of Choline Transporter Surface Expression and Phosphorylation by Protein Kinase C and Protein Phosphatase 1/2A J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 536 - 545. [Abstract] [Full Text] [PDF]

				R. A. Vaughan Phosphorylation and Regulation of Psychostimulant-Sensitive Neurotransmitter Transporters J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 1 - 7. [Abstract] [Full Text] [PDF]

				L.-B. Li, N. Chen, S. Ramamoorthy, L. Chi, X.-N. Cui, L. C. Wang, and M. E. A. Reith The Role of N-Glycosylation in Function and Surface Trafficking of the Human Dopamine Transporter J. Biol. Chem., May 14, 2004; 279(20): 21012 - 21020. [Abstract] [Full Text] [PDF]