Caveolin-1 Interacts with 5-HT2A Serotonin Receptors and Profoundly Modulates the Signaling of Selected Gαq-coupled Protein Receptors
作者： Anushree Bhatnagar , Douglas J. Sheffler , Wesley K. Kroeze , BethAnn Compton-Toth , Bryan L. Roth
关键词:
摘要: 5-Hydroxytryptamine 2A (5-HT2A) serotonin receptors are important for a variety of functions including vascular smooth muscle contraction, platelet aggregation, and the modulation perception, cognition, emotion. In search 5-HT2A receptor-interacting proteins, we discovered that caveolin-1 (Cav-1), scaffolding protein enriched in caveolae, complexes with number cell types C6 glioma cells, transfected HEK-293 rat brain synaptic membrane preparations. To address functional significance this interaction, performed RNA interference-mediated knockdown Cav-1 type endogenously expresses both Cav-1. We vitro cells nearly abolished receptor-mediated signal transduction as measured by calcium flux assays. also greatly attenuated endogenous Gαq-coupled P2Y purinergic signaling without altering PAR-1 thrombin receptors. appeared to modulate facilitating interaction Gαq. These studies provide compelling evidence prominent role regulating activity not only but selected
sci-hub.se 参考文章(42)
John A Gray, Bryan L Roth, A Last GASP for GPCRs Science. ,vol. 297, pp. 529- 531 ,(2002) , 10.1126/SCIENCE.1075453
Kristen L. Pierce, Richard T. Premont, Robert J. Lefkowitz, Seven-transmembrane receptors. Nature Reviews Molecular Cell Biology. ,vol. 3, pp. 639- 650 ,(2002) , 10.1038/NRM908
X.M. Guan, T.S. Kobilka, B.K. Kobilka, Enhancement of membrane insertion and function in a type IIIb membrane protein following introduction of a cleavable signal peptide. Journal of Biological Chemistry. ,vol. 267, pp. 21995- 21998 ,(1992) , 10.1016/S0021-9258(18)41623-7
Babak Razani, Jeffery A Engelman, Xiao Bo Wang, William Schubert, Xiao Lan Zhang, Carolyn B Marks, Frank Macaluso, Robert G Russell, Maomi Li, Richard G Pestell, Dolores Di Vizio, Harry Hou, Burkhard Kneitz, Guy Lagaud, George J Christ, Winfried Edelmann, Michael P Lisanti, None, Caveolin-1 Null Mice Are Viable but Show Evidence of Hyperproliferative and Vascular Abnormalities Journal of Biological Chemistry. ,vol. 276, pp. 38121- 38138 ,(2001) , 10.1074/JBC.M105408200
Jacques Couet, Massimo Sargiacomo, Michael P. Lisanti, Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins: CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIES * Journal of Biological Chemistry. ,vol. 272, pp. 30429- 30438 ,(1997) , 10.1074/JBC.272.48.30429
William Schubert, Philippe G. Frank, Scott E. Woodman, Hideyuki Hyogo, David E. Cohen, Chi-Wing Chow, Michael P. Lisanti, Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. Journal of Biological Chemistry. ,vol. 277, pp. 40091- 40098 ,(2002) , 10.1074/JBC.M205948200
Sergey V. Matveev, Eric J. Smart, Heterologous desensitization of EGF receptors and PDGF receptors by sequestration in caveolae American Journal of Physiology-cell Physiology. ,vol. 282, ,(2002) , 10.1152/AJPCELL.00349.2001
B. L. Roth, K. Baner, R. Westkaemper, D. Siebert, K. C. Rice, S. Steinberg, P. Ernsberger, R. B. Rothman, Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 11934- 11939 ,(2002) , 10.1073/PNAS.182234399
Douglas J. Sheffler, Bryan L. Roth, Salvinorin A: the ‘magic mint’ hallucinogen finds a molecular target in the kappa opioid receptor Trends in Pharmacological Sciences. ,vol. 24, pp. 107- 109 ,(2003) , 10.1016/S0165-6147(03)00027-0
Caroline Saucier, Paul R. Albert, Identification of an Endogenous 5-Hydroxytryptamine2A Receptor in NIH-3T3 Cells: Agonist-Induced Down-Regulation Involves Decreases in Receptor RNA and Number Journal of Neurochemistry. ,vol. 68, pp. 1998- 2011 ,(2002) , 10.1046/J.1471-4159.1997.68051998.X