Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

被引:45
作者
Allen, John A. [1 ]
Yadav, Prern N. [1 ]
Roth, Bryan L. [1 ]
机构
[1] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
5-HT2A; 5-Hydroxytryptamine; Serotonin; PSD95; Arrestin; Caveolin; Lipid raft; RSK2; PKC; GPCR; Gq; PDZ; Post-synaptic density; Desensitization; Trafficking; Endocytosis; Internalization; Scaffolding;
D O I
10.1016/j.neuropharm.2008.06.048
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
5-HT2A serotonin receptors are essential molecular targets for the actions of LSD-like hallucinogens and atypical antipsychotic drugs. 5-HT2A serotonin receptors also mediate a variety of physiological processes in peripheral and central nervous systems including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. Scaffolding proteins have emerged as important regulators of 5-HT2A receptors and our recent studies suggest multiple scaffolds exist for 5-HT2A receptors including PSD95, arrestin, and caveolin. In addition, a novel interaction has emerged between p90 ribosomal S6 kinase and 5-HT2A receptors which attenuates receptor signaling. This article reviews our recent studies and emphasizes the role of scaffolding proteins and kinases in the regulation of 5-HT2A trafficking, targeting and signaling. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:961 / 968
页数:8
相关论文
共 94 条
[21]   Cholesterol depletion disrupts caveolae and differentially impairs agonist-induced arterial contraction [J].
Dreja, K ;
Voldstedlund, M ;
Vinten, J ;
Tranum-Jensen, J ;
Hellstrand, P ;
Swärd, K .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (08) :1267-1272
[22]  
Ferguson SSG, 2001, PHARMACOL REV, V53, P1
[23]   Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization [J].
Ferguson, SSG ;
Downey, WE ;
Colapietro, AM ;
Barak, LS ;
Menard, L ;
Caron, MG .
SCIENCE, 1996, 271 (5247) :363-366
[24]   Desensitization of G protein-coupled receptors and neuronal functions [J].
Gainetdinov, RR ;
Premont, RT ;
Bohn, LM ;
Lefkowitz, RJ ;
Caron, MG .
ANNUAL REVIEW OF NEUROSCIENCE, 2004, 27 :107-144
[25]   Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor:: The third intracellular loop is α-helical and binds purified arrestins [J].
Gelber, EI ;
Kroeze, WK ;
Willins, DL ;
Gray, JA ;
Sinar, CA ;
Hyde, EG ;
Gurevich, V ;
Benovic, J ;
Roth, BL .
JOURNAL OF NEUROCHEMISTRY, 1999, 72 (05) :2206-2214
[26]  
GLENNON RA, 1990, NEUROPSYCHOPHARMACOL, V3, P509
[27]   Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior [J].
Gonzalez-Maeso, Javier ;
Weisstaub, Noelia V. ;
Zhou, Mingming ;
Chan, Pokman ;
Ivic, Lidija ;
Ang, Rosalind ;
Lira, Alena ;
Bradley-Moore, Maria ;
Ge, Yongchao ;
Zhou, Qiang ;
Sealfon, Stuart C. ;
Gingrich, Jay A. .
NEURON, 2007, 53 (03) :439-452
[28]   beta-arrestin acts as a clathrin adaptor in endocytosis of the beta(2)-adrenergic receptor [J].
Goodman, OB ;
Krupnick, JG ;
Santini, F ;
Gurevich, VV ;
Penn, RB ;
Gagnon, AW ;
Keen, JH ;
Benovic, JL .
NATURE, 1996, 383 (6599) :447-450
[29]   Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization [J].
Gray, JA ;
Compton-Toth, BA ;
Roth, BL .
BIOCHEMISTRY, 2003, 42 (36) :10853-10862
[30]   The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT2A receptor induces agonist-independent internalization [J].
Gray, JA ;
Bhatnagar, A ;
Gurevich, VV ;
Roth, BL .
MOLECULAR PHARMACOLOGY, 2003, 63 (05) :961-972