박주민 (제주대학교 의과대학, Johns Hopkins University School of Medicine) | 한빛사논문 > 한빛사

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제주대학교 의과대학, Johns Hopkins University School of Medicine

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Cell, Volume 154, Issue 3, 637-650, 1 August 2013 | 10.1016/j.cell.2013.07.001 A Prolyl-Isomerase Mediates Dopamine-Dependent Plasticity and Cocaine Motor Sensitization

Abstract

Joo Min Park,^1,6,7 Jia-Hua Hu,^1,7 Aleksandr Milshteyn,^3,7 Ping-Wu Zhang,¹ Chester G. Moore,¹ Sungjin Park,¹ Michael C. Datko,⁴ Racquel D. Domingo,⁴ Cindy M. Reyes,⁴ Xiaodong J. Wang,⁵ Felicia A. Etzkorn,⁵ Bo Xiao,¹ Karen K. Szumlinski,⁴ Dorothee Kern,³ David J. Linden,¹ and Paul F. Worley^1,2,*

¹Department of Neuroscience
²Department of Neurology
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
³Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02452, USA
⁴Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California, Santa Barbara,
CA 93106, USA
⁵Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA
⁶Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, South Korea
⁷These authors contributed equally to this work

^*Correspondence: Paul F. Worley

Summary
Synaptic plasticity induced by cocaine and other drugs underlies addiction. Here we elucidate molecular events at synapses that cause this plasticity and the resulting behavioral response to cocaine in mice. In response to D1-dopamine-receptor signaling that is induced by drug administration, the glutamate-receptor protein metabotropic glutamate receptor 5 (mGluR5) is phosphorylated by microtubule-associated protein kinase (MAPK), which we show potentiates Pin1-mediated prolyl-isomerization of mGluR5 in instances where the product of an activity-dependent gene, Homer1a, is present to enable Pin1-mGluR5 interaction. These biochemical events potentiate N-methyl-D-aspartate receptor (NMDAR)-mediated currents that underlie synaptic plasticity and cocaine-evoked motor sensitization as tested in mice with relevant mutations. The findings elucidate how a coincidence of signals from the nucleus and the synapse can render mGluR5 accessible to activation with consequences for drug-induced dopamine responses and point to depotentiation at corticostriatal synapses as a possible therapeutic target for treating addiction.

논문정보

형식Research article
게재일2013년 08월 (BRIC 등록일 2013-08-06)
연구진국내+국외 연구진
분야 의약학 > 신경의학

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