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

来源：

NEUROPHARMACOLOGY | 2008年 / 55卷 / 06期

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

页码：961 / 968

页数：8

共 94 条

[31] Cell biology - A last GASP for GPCRs? [J].

Gray, JA ;

Roth, BL .

SCIENCE, 2002, 297 (5581) :529-531

[32] Paradoxical trafficking and regulation of 5HT2A receptors by agonists and antagonists [J].

Gray, JA ;

Roth, BL .

BRAIN RESEARCH BULLETIN, 2001, 56 (05) :441-451

[33] Cell-type specific effects of endocytosis inhibitors on 5-Hydroxytryptamine2A receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells [J].

Gray, JA ;

Sheffler, DJ ;

Bhatnagar, A ;

Woods, JA ;

Hufeisen, SJ ;

Benovic, JL ;

Roth, BL .

MOLECULAR PHARMACOLOGY, 2001, 60 (05) :1020-1030

[34] Molecular targets for treating cognitive dysfunction in schizophrenia [J].

Gray, John A. ;

Roth, Bryan L. .

SCHIZOPHRENIA BULLETIN, 2007, 33 (05) :1100-1119

[35] Coffin-Lowry syndrome: clinical and molecular features [J].

Hanauer, A ;

Young, ID .

JOURNAL OF MEDICAL GENETICS, 2002, 39 (10) :705-713

[36] Mechanisms of ligand-induced desensitization of the 5-hydroxytryptamine2A receptor [J].

Hanley, NRS ;

Hensler, JG .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 300 (02) :468-477

[37] β1-adrenergic receptor association with PSD-95 -: Inhibition of receptor internalization and facilitation of β1-adrenergic receptor interaction with N-methyl-D-aspartate receptors [J].

Hu, LYA ;

Tang, YT ;

Miller, WE ;

Cong, M ;

Lau, AG ;

Lefkowitz, RJ ;

Hall, RA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (49) :38659-38666

[38] Autoregulatory mechanisms in protein-tyrosine kinases [J].

Hubbard, SR ;

Mohammadi, M ;

Schlessinger, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (20) :11987-11990

[39] Binding of neuroligins to PSD-95 [J].

Irie, M ;

Hata, Y ;

Takeuchi, M ;

Ichtchenko, K ;

Toyoda, A ;

Hirao, K ;

Takai, Y ;

Rosahl, TW ;

Sudhof, TC .

SCIENCE, 1997, 277 (5331) :1511-1515

[40] 5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex:: Possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites [J].

Jakab, RL ;

Goldman-Rakic, PS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :735-740

← 1 2 3 4 5 6 7 8 9 10 →