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Originally published In Press as doi:10.1074/jbc.M011588200 on February 5, 2001

J. Biol. Chem., Vol. 276, Issue 18, 15208-15215, May 4, 2001
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Two Novel Xenopus Homologs of Mammalian LPA1/EDG-2 Function as Lysophosphatidic Acid Receptors in Xenopus Oocytes and Mammalian Cells*

Yuka KimuraDagger , Anja Schmitt§, Nobuyuki FukushimaDagger , Isao IshiiDagger , Hideo Kimura, Angel R. Nebreda§, and Jerold ChunDagger ||**

From the Dagger  Department of Pharmacology and || Neurosciences and Biomedical Sciences Programs, School of Medicine, University of California, San Diego, La Jolla, California 92093-0636, the § European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany, and the  Division of Molecular Genetics, National Institute of Neuroscience, Kodaira, Tokyo 187-8502, Japan

Lysophosphatidic acid (LPA) induces diverse biological responses in many types of cells and tissues by activating its specific G protein-coupled receptors (GPCRs). Previously, three cognate LPA GPCRs (LPA1/VZG-1/EDG-2, LPA2/EDG-4, and LPA3/EDG-7) were identified in mammals. By contrast, an unrelated GPCR, PSP24, was reported to be a high affinity LPA receptor in Xenopus laevis oocytes, raising the possibility that Xenopus uses a very different form of LPA signaling. Toward addressing this issue, we report two novel Xenopus genes, xlpA1-1 and xlpA1-2, encoding LPA1 homologs (~90% amino acid sequence identity with mammalian LPA1). Both xlpA1-1 and xlpA1-2 are expressed in oocytes and the nervous system. Overexpression of either gene in oocytes potentiated LPA-induced oscillatory chloride ion currents through a pertussis toxin-insensitive pathway. Injection of antisense oligonucleotides designed to inhibit xlpA1-1 and xlpA1-2 expression in oocytes eliminated their endogenous response to LPA. Furthermore, retrovirus-mediated heterologous expression of xlpA1-1 or xlpA1-2 in B103 rat neuroblastoma cells that are unresponsive to LPA conferred LPA-induced cell rounding and adenylyl cyclase inhibition. These results indicate that XLPA1-1 and XLPA1-2 are functional Xenopus LPA receptors and demonstrate the evolutionary conservation of LPA signaling over a range of vertebrate phylogeny.

* This work was supported by grants from the National Institute of Mental Health (to J. C.), the National Institute of Neuroscience, Japan (to H. K.), and the Uehara Memorial Foundation (to N. F. and I. I.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequences reported in this paper have been submitted to the EMBL/GenBankTM/EBI Data Bank with accession numbers AJ249843 and AJ249844.

** To whom correspondence should be addressed: Dept. of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0636. Tel.: 858-534-2659; Fax: 858-534-8242; E-mail: jchun@ucsd.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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