title: Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A.
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.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Caius G
authors.initials: CG
authors.lastname: Radu
authors.forename: Li V
authors.initials: LV
authors.lastname: Yang
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Bentolila
authors.forename: Mireille
authors.initials: M
authors.lastname: Riedinger
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006825:Hybridomas; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D051379:Mice; D018613:Microscopy, Confocal; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism; D041701:Swiss 3T3 Cells
chemical_list: D018797:Cell Cycle Proteins; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
references.citation: Biochim Biophys Acta. 2002 May 23;1582(1-3):168-74
references.pmid: 12069825
references.citation: Nat Rev Mol Cell Biol. 2002 Sep;3(9):639-50
references.pmid: 12209124
references.citation: Trends Endocrinol Metab. 2002 Oct;13(8):336-43
references.pmid: 12217490
references.citation: Biochemistry. 2002 Oct 8;41(40):11981-9
references.pmid: 12356298
references.citation: Nat Rev Drug Discov. 2002 Oct;1(10):808-20
references.pmid: 12360258
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2002 Nov;366(5):381-416
references.pmid: 12382069
references.citation: Mol Pharmacol. 2003 Jan;63(1):9-18
references.pmid: 12488531
references.citation: Blood. 2003 Jan 15;101(2):399-406
references.pmid: 12393663
references.citation: Nature. 2003 Mar 6;422(6927):37-44
references.pmid: 12621426
references.citation: J Biol Chem. 2003 Apr 4;278(14):12222-30
references.pmid: 12529370
references.citation: J Biol Chem. 2003 Apr 18;278(16):14379-86
references.pmid: 12586833
references.citation: Free Radic Biol Med. 1990;9(2):155-68
references.pmid: 2227530
references.citation: Semin Immunol. 1991 Sep;3(5):283-97
references.pmid: 1686832
references.citation: J Cell Biol. 1992 Apr;117(2):279-90
references.pmid: 1373141
references.citation: Biochem J. 1992 Apr 1;283 ( Pt 1):1-19
references.pmid: 1314560
references.citation: Mol Pharmacol. 1994 Mar;45(3):517-23
references.pmid: 8145736
references.citation: Trends Pharmacol Sci. 1994 Jun;15(6):170-2
references.pmid: 8091507
references.citation: J Cell Biol. 1994 Nov;127(4):915-34
references.pmid: 7962076
references.citation: DNA Cell Biol. 1995 Jan;14(1):25-35
references.pmid: 7832990
references.citation: J Gen Physiol. 1994 Oct;104(4):645-73
references.pmid: 7530766
references.citation: Cell Immunol. 1996 Feb 25;168(1):78-84
references.pmid: 8599842
references.citation: J Biol Chem. 1996 Oct 11;271(41):25406-11
references.pmid: 8810308
references.citation: Exp Cell Res. 1999 Nov 25;253(1):230-8
references.pmid: 10579925
references.citation: Biochem J. 2000 Jan 1;345 Pt 1:61-7
references.pmid: 10600639
references.citation: Mol Pharmacol. 2000 Feb;57(2):219-31
references.pmid: 10648631
references.citation: FEBS Lett. 2000 Jan 28;466(2-3):300-4
references.pmid: 10682848
references.citation: Mol Pharmacol. 2000 Apr;57(4):659-66
references.pmid: 10727510
references.citation: Mol Pharmacol. 2000 May;57(5):890-8
references.pmid: 10779371
references.citation: Nat Cell Biol. 2000 May;2(5):261-7
references.pmid: 10806476
references.citation: Curr Opin Lipidol. 2000 Jun;11(3):267-75
references.pmid: 10882342
references.citation: Trends Pharmacol Sci. 2000 Aug;21(8):304-8
references.pmid: 10918636
references.citation: Oncogene. 2000 Aug 10;19(34):3866-77
references.pmid: 10951580
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12109-14
references.pmid: 11050239
references.citation: Mol Endocrinol. 2001 Jan;15(1):149-63
references.pmid: 11145746
references.citation: Pharmacol Rev. 2001 Mar;53(1):1-24
references.pmid: 11171937
references.citation: J Cell Biol. 2001 Apr 16;153(2):429-34
references.pmid: 11309421
references.citation: Immunity. 2001 May;14(5):561-71
references.pmid: 11371358
references.citation: J Cell Sci. 2003 May 15;116(Pt 10):1969-80
references.pmid: 12668728
references.citation: Genes Dev. 2003 May 15;17(10):1240-52
references.pmid: 12730121
references.citation: Curr Biol. 2003 Jul 15;13(14):R574-6
references.pmid: 12867054
references.citation: Nature. 2003 Sep 4;425(6953):93-8
references.pmid: 12955148
references.citation: J Cell Biol. 1996 Nov;135(4):913-24
references.pmid: 8922376
references.citation: J Biol Chem. 1996 Dec 20;271(51):32874-80
references.pmid: 8955127
references.citation: J Biol Chem. 1997 Jun 6;272(23):14817-24
references.pmid: 9169450
references.citation: J Exp Med. 1997 Jul 7;186(1):153-8
references.pmid: 9207004
references.citation: J Biol Chem. 1998 Aug 28;273(35):22161-4
references.pmid: 9712825
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12334-9
references.pmid: 9770487
references.citation: EMBO J. 1999 Apr 1;18(7):1723-9
references.pmid: 10202136
references.citation: Lupus. 1999;8(3):220-6
references.pmid: 10342715
references.citation: Science. 2005 Jan 14;307(5707):206
references.pmid: 15653487
references.citation: Blood. 2005 Feb 1;105(3):1127-34
references.pmid: 15383458
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1632-7
references.pmid: 15665078
references.citation: J Biol Chem. 1997 Jan 3;272(1):5-8
references.pmid: 8995214
references.citation: Life Sci. 2003 Dec 5;74(2-3):217-24
references.pmid: 14607249
references.citation: Mol Pharmacol. 2003 Dec;64(6):1271-6
references.pmid: 14645655
references.citation: Endocr Rev. 2003 Dec;24(6):765-81
references.pmid: 14671004
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):245-50
references.pmid: 14681556
references.citation: Sci STKE. 2004 Jan 13;2004(215):pe1
references.pmid: 14722344
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:559-609
references.pmid: 14744258
references.citation: J Cell Sci. 2004 Feb 15;117(Pt 5):723-34
references.pmid: 14734649
references.citation: Annu Rev Biochem. 2004;73:321-54
references.pmid: 15189145
references.citation: Cell Signal. 2004 Sep;16(9):975-81
references.pmid: 15212758
references.citation: Science. 2004 Jun 25;304(5679):1940-4
references.pmid: 15218143
references.citation: Mol Pharmacol. 2004 Oct;66(4):843-54
references.pmid: 15258254
references.citation: J Biol Chem. 2004 Oct 8;279(41):42484-91
references.pmid: 15280385
references.citation: J Biol Chem. 1981 Feb 25;256(4):1522-4
references.pmid: 7462211
references.citation: J Cyclic Nucleotide Protein Phosphor Res. 1986;11(1):35-46
references.pmid: 3009570
references.citation: J Cell Biol. 1989 Feb;108(2):389-400
references.pmid: 2563728
references.citation: Biochim Biophys Acta. 1990 May 7;1031(2):225-46
references.pmid: 2160275
references.citation: Biochem Biophys Res Commun. 2001 Jun 15;284(3):596-601
references.pmid: 11396942
references.citation: Science. 2001 Jul 27;293(5530):702-5
references.pmid: 11474113
references.citation: Mol Pharmacol. 2001 Dec;60(6):1243-53
references.pmid: 11723231
references.citation: Mol Cell. 2001 Dec;8(6):1327-38
references.pmid: 11779507
references.citation: J Biol Chem. 2002 Feb 22;277(8):5891-901
references.pmid: 11729186
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7877-82
references.pmid: 12060735