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The Serotonin 5-HT2A and 5-HT2C Receptors Interact with Specific Sets of PDZ Proteins
Open accessAbstract
The 5-hydroxytryptamine type 2A (5-HT(2A)) receptor and the 5-HT(2C) receptor are closely related members of the G-protein-coupled receptors activated by serotonin that share very similar pharmacological profiles and cellular signaling pathways. These receptors express a canonical class I PDZ ligand (SXV) at their C-terminal extremity. Here, we have identified proteins that interact with the PDZ ligand of the 5-HT(2A) and 5-HT(2C) receptors by a proteomic approach associating affinity chromatography using immobilized synthetic peptides encompassing the PDZ ligand and mass spectrometry. We report that both receptor C termini interact with specific sets of PDZ proteins in vitro. The 5-HT(2C) receptor but not the 5-HT(2A) receptor binds to the Veli-3.CASK.Mint1 ternary complex and to SAP102. In addition, the 5-HT(2C) receptor binds more strongly to PSD-95 and MPP-3 than the 5-HT(2A) receptor. In contrast, a robust interaction between the 5-HT(2A) receptor and the channel-interacting PDZ protein CIPP was found, whereas CIPP did not significantly associate with the 5-HT(2C) receptor. We also show that residues located at the -1 position and upstream the PDZ ligand in the C terminus of the 5-HT(2A) and 5-HT(2C) receptors are major determinants in their interaction with specific PDZ proteins. Immunofluorescence and electron microscopy studies strongly suggested that these specific interactions also take place in living cells and that the 5-HT(2) receptor-PDZ protein complexes occur in intracellular compartments. The interaction of the 5-HT(2A) and the 5-HT(2C) receptor with specific sets of PDZ proteins may contribute to their different signal transduction properties.
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Cites
Butz, S., Okamoto, M., & Südhof, T. C. (1998) · Cell · doi:10.1016/s0092-8674(00)81736-5 · Cited by 548
Serotonin model of schizophrenia: emerging role of glutamate mechanisms
Aghajanian, G. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00046-6 · Cited by 529
NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex
Sans, N., Prybylowski, K., Petralia, R. S., Chang, K., Wang, Y.-X., Racca, C., Vicini, S., & Wenthold, R. J. (2003) · Nature Cell Biology · doi:10.1038/ncb990 · Cited by 327
Miner, L. A. H., Backstrom, J. R., Sanders-Bush, E., & Sesack, S. R. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00580-8 · Cited by 216
Cited by
Lesch, K.-P., & Waider, J. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.013 · Cited by 435
Regulation of GPCR activity, trafficking and localization by GPCR‐interacting proteins
Magalhaes, A. C., Dunn, H., & Ferguson, S. S. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01552.x · Cited by 353
Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways
López-Giménez, J. F., & González-Maeso, J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_478 · Cited by 299
Rapid modulation of spine morphology by the 5-HT 2A serotonin receptor through kalirin-7 signaling
Jones, K. A., Srivastava, D. P., Allen, J. A., Strachan, R. T., Roth, B. L., & Penzes, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905884106 · Cited by 226
Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice
Brunskill, E. W., Ehrman, L. A., Williams, M. T., Klanke, J., Hammer, D., Schaefer, T. L., Sah, R., Il, G. W. D., Potter, S. S., & Vorhees, C. V. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04291.x · Cited by 84
Metadata
- Authors
- Bécamel, C., Gavarini, S., Chanrion, B., Alonso, G., Galéotti, N., Dumuis, A., Bockaert, J., & Marin, P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 279
- Issue
- 19
- Pages
- 20257-20266
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2079882316
- Cited by
- 170
- References
- 4
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bécamel, C., Gavarini, S., Chanrion, B., Alonso, G., Galéotti, N., Dumuis, A., Bockaert, J., & Marin, P. (2004). The Serotonin 5-HT2A and 5-HT2C Receptors Interact with Specific Sets of PDZ Proteins. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m312106200
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
