Disease relevance of Edg2

• Pertussis toxin, the LPA1/LPA3 receptor-selective antagonist dioctylglycerol pyrophosphate, the myristoylated inhibitory pseudosubstrate peptide of protein kinase A (PKI), Wortmannin and PD98059 abolished the neurite-promoting effect. cPA elicited a sustained activation of extracellular signal-related kinases (ERK) 1/2 and Akt [1].
• These results suggest that LPA receptor signaling may play an important role in neuroprotection in retinal ischemia-reperfusion injury [2].
• We then examined the biological activity of 2-arachidonoyl LPA and compared it with that of 2-AG using neuroblastoma x glioma hybrid NG108-15 cells which express both the LPA receptor and cannabinoid CB1 receptor [3].
• The role of H2O2 and the lactoperoxidase-SCN(-)-H2O2 system on the interaction between two bacteria originating from human dental plaque, Streptococcus rattus (mutans) BHT and Streptococcus mitior LPA-1, grown on human teeth in an artificial mouth [4].

High impact information on Edg2

• Serum-induced membrane depolarization in quiescent fibroblasts: activation of a chloride conductance through the G protein-coupled LPA receptor [5].
• Overexpression of functional epitope-tagged LPA1/VZG-1 protein decreases SC apoptosis in response to serum withdrawal [6].
• In the presence of N-palmitoyl L-serine phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss of confluence in vitro and the hydraulic permeability caused by 5 microM LPA in vivo were abolished [7].
• Thus, the multiple effects of LPA in Schwann cells (actin reorganization, survival, and myelin gene expression) appear to be mediated through the different G protein-dependent pathways activated by the LPA receptor [8].
• Oligodendroglial expression of Edg-2 receptor: developmental analysis and pharmacological responses to lysophosphatidic acid [9].

Biological context of Edg2

• By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors [10].
• Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life [10].
• As a first application to molecular genetic studies, they were used to exclude the Edg-2 gene in six families with phenotype of demyelinating Charcot-Marie-Tooth disease of unknown origin [11].
• Three mammalian LPA receptor (LPAr) subtypes have been identified by molecular cloning, named lp(A1), lp(A2) and lp(A3), that are coupled to heterotrimeric G-proteins for signal transduction [12].
• We conclude that S-1-P, through an LPA receptor-independent mechanism, stimulates two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of adenylyl cyclase, through distinct S-1-P receptor-transducer systems, resulting in the modulation of glycogenolysis in rat hepatocytes [13].

Anatomical context of Edg2

• Therefore, in contrast to other cell types, in which LPA exerts pleiotropic effects, Edg-2-positive postmitotic oligodendrocytes display a restricted responsiveness to LPA [9].
• In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves [10].
• Consequently, we have developed an assay that monitors definitively Edg2 receptor-mediated responses in a mammalian cell line [14].
• This suggests a possible role for the Edg2 receptor in nerve cell myelination [15].
• Rat primary chondrocytes express the lysophosphatidic acid (LPA) receptor, LPA1, LPA3, but not LPA2 [16].

Associations of Edg2 with chemical compounds

• The levels of mRNA of LPA1 and S1P receptors was reduced by overnight exposure to S1P, while the same treatment significantly up-regulated the level of LPA3 mRNA [17].
• We have now identified two splice variants of Edg-2 mRNA in rat brain that encode two receptor isoforms differing by a stretch of 18 amino acids in the NH2-terminal extracellular tail of the receptor [11].
• First, the RGDS peptide, which blocks cell matrix-induced integrin clustering and cytoskeletal rearrangement, reduced the number of cells containing LPA1 in the nucleus [18].
• In initial 48 h experiments, teeth were inoculated with Streptococcus rattus BHT or 'Streptococcus mitior' LPA-1 in pure culture and provided with 1% (w/v) glucose for 1 h every 6 h [19].
• Suramin, an LPA receptor antagonist, abolished the induction of preproET-1 mRNA by LPA [20].

Regulatory relationships of Edg2

• One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes [10].

Other interactions of Edg2

• This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker [10].
• Initially, we observed that OECs expressed the genes for LPA1, LPA2, and LPA3 receptors [21].

Analytical, diagnostic and therapeutic context of Edg2

• RT-PCR and Western blot analyses indicate that oligodendrocyte precursors and mature oligodendrocytes express mRNA and protein for LPA1, one of several LPA receptors [22].
• Myocytes express mRNA for all three G-protein-coupled LPA receptor subtypes (LPA(1)/Edg-2, LPA(2)/Edg-4, and LPA(3)/Edg-7) as indicated by RT-PCR analysis [23].
• To determine whether LPA may also act at the level of the spinal cord, LPA receptor G-protein coupling in lumbar spinal cord sections was studied with in vitro autoradiography of guanylyl 5'-[g-[(35)S]thio]triphosphate ([(35)S]GTPgammaS) binding [24].
• We found that the LPA receptor was most dominantly expressed in rat astrocytes, determined by LPA-induced Ca2+ imaging, and by Northern blot analyses [25].

References