Lysophosphatidylcholine-induced Surface Redistribution Regulates Signaling of the Murine G Protein-coupled Receptor G2A
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Published:2005-05
Issue:5
Volume:16
Page:2234-2247
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ISSN:1059-1524
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Container-title:Molecular Biology of the Cell
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language:en
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Short-container-title:MBoC
Author:
Wang Li1, Radu Caius G.1, Yang Li V.2, Bentolila Laurent A.3, Riedinger Mireille2, Witte Owen N.12
Affiliation:
1. Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095 2. Howard Hughes Medical Institute/UCLA, UCLA, Los Angeles, CA 90095 3. Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095
Abstract
Intracellular trafficking and spatial dynamics of membrane receptors critically regulate receptor function. Using microscopic and subcellular fractionation analysis, we studied the localization of the murine G protein-coupled receptor G2A (muG2A). Evaluating green fluorescent protein-tagged, exogenously expressed as well as the endogenous muG2A, we observed that this receptor was spontaneously internalized and accumulated in endosomal compartments, whereas its surface expression was enhanced and stabilized by lysophosphatidylcholine (LPC) treatment. Monensin, a general inhibitor of recycling pathways, blocked LPC-regulated surface localization of muG2A as well as muG2A-dependent extracellular signal-regulated kinase (ERK) activation and cell migration induced by LPC treatment. Mutation of the conserved DRY motif (R→ A) enhanced the surface expression of muG2A, resulting in its resistance to monensin inhibition of ERK activation. Our data suggest that intracellular sequestration and surface expression regulated by LPC, rather than direct agonistic activity control the signaling responses of murine G2A toward LPC.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
Reference75 articles.
1. Acharya, S., and Karnik, S. S. (1996). Modulation of GDP release from transducin by the conserved Glu134-Arg135 sequence in rhodopsin.J. Biol. Chem.271, 25406–25411. 2. Alewijnse, A. E., Timmerman, H., Jacobs, E. H., Smit, M. J., Roovers, E., Cotecchia, S., and Leurs, R. (2000). The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H(2) receptor.Mol. Pharmacol.57, 890–898. 3. Bockaert, J., and Pin, J. P. (1999). Molecular tinkering of G protein-coupled receptors: an evolutionary success.EMBO J.18, 1723–1729. 4. Cabrera-Vera, T. M., Vanhauwe, J., Thomas, T. O., Medkova, M., Preininger, A., Mazzoni, M. R., and Hamm, H. E. (2003). Insights into G protein structure, function, and regulation.Endocr. Rev.24, 765–781. 5. Campbell, R. E., Tour, O., Palmer, A. E., Steinbach, P. A., Baird, G. S., Zacharias, D. A., and Tsien, R. Y. (2002). A monomeric red fluorescent protein.Proc. Natl. Acad. Sci. USA99, 7877–7882.
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