Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A.
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.
Wang
Li
L
Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.
Radu
Caius G
CG
Yang
Li V
LV
Bentolila
Laurent A
LA
Riedinger
Mireille
M
Witte
Owen N
ON
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
D018797:Cell Cycle Proteins; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
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