Two novel Xenopus homologs of mammalian LP(A1)/EDG-2 function as lysophosphatidic acid receptors in Xenopus oocytes and mammalian cells.

Abstract

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 (LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/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, xlp(A1)-1 and xlp(A1)-2, encoding LP(A1) homologs (approximately 90% amino acid sequence identity with mammalian LP(A1)). Both xlp(A1)-1 and xlp(A1)-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 xlp(A1)-1 and xlp(A1)-2 expression in oocytes eliminated their endogenous response to LPA. Furthermore, retrovirus-mediated heterologous expression of xlp(A1)-1 or xlp(A1)-2 in B103 rat neuroblastoma cells that are unresponsive to LPA conferred LPA-induced cell rounding and adenylyl cyclase inhibition. These results indicate that XLP(A1)-1 and XLP(A1)-2 are functional Xenopus LPA receptors and demonstrate the evolutionary conservation of LPA signaling over a range of vertebrate phylogeny.

• Authors: Y Kimura, A Schmitt, N Fukushima, I Ishii, H Kimura, A R Nebreda, J Chun
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 18 Pg. 15208-15 (May 04 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11278944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adenylate Cyclase Toxin
• DNA, Complementary
• Nuclear Proteins
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• Receptors, Lysophosphatidic Acid
• Transcription Factors
• Virulence Factors, Bordetella
• Pertussis Toxin
• GTP-Binding Proteins

Topics

• Adenylate Cyclase Toxin
• Amino Acid Sequence
• Animals
• Base Sequence
• Cloning, Molecular
• DNA, Complementary
• GTP-Binding Proteins (metabolism)
• Molecular Sequence Data
• Nuclear Proteins (chemistry, genetics, metabolism)
• Oocytes (drug effects, metabolism)
• Pertussis Toxin
• Receptors, Cell Surface (chemistry, genetics, metabolism)
• Receptors, G-Protein-Coupled
• Receptors, Lysophosphatidic Acid
• Sequence Homology, Amino Acid
• Transcription Factors (chemistry, genetics, metabolism)
• Virulence Factors, Bordetella (pharmacology)
• Xenopus