Synaptic multiprotein complexes associated with 5-HT2C receptors:: a proteomic approach

被引:122
作者
Bécamel, C
Alonso, G
Geléotti, N
Demey, E
Jouin, P
Ullmer, C
Dumuis, A
Bockaert, J
Marin, P [1 ]
机构
[1] CNRS, UPR 9023, F-34094 Montpellier 05, France
[2] CNRS, UMR 5101, CCIPE, F-34094 Montpellier, France
[3] Biofrontera Pharmaceut GmbH, D-51377 Leverkusen, Germany
关键词
5-HT2C receptor; PDZ domain; proteomic; analysis; scaffold protein;
D O I
10.1093/emboj/21.10.2332
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Membrane-bound receptors such as tyrosine kinases and ionotropic receptors are associated with large protein networks structured by protein-protein interactions involving multidomain proteins. Although these networks have emerged as a general mechanism of cellular signalling, much less is known about the protein complexes associated with G-protein-coupled receptors (GPCRs). Using a proteomic approach based on peptide affinity chromatography followed by mass spectrometry and immunoblotting, we have identified 15 proteins that interact with the C-terminal tail of the 5-hydroxytryptamine 2C (5-HT2C) receptor, a GPCR. These proteins include several synaptic multidomain proteins containing one or several PDZ domains (PSD95 and the proteins of the tripartite complex Veli3-CASK-Mint1), proteins of the actin/spectrin cytoskeleton and signalling proteins. Coimmunoprecipitation experiments showed that 5-HT2C receptors interact with PSD95 and the Veli3-CASK-Mint1 complex in vivo. Electron microscopy also indicated a synaptic enrichment of Veli3 and 5-HT2C receptors and their colocalization in microvilli of choroidal cells. These results indicate that the 5-HT2C receptor is associated with protein networks that are important for its synaptic localization and its coupling to the signalling machinery.
引用
收藏
页码:2332 / 2342
页数:11
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