The lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) receptor gene families: cloning and comparative expression analysis in Xenopus laevis

Abstract

Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are endogenous bioactive lipids which mediate a variety of biological cell responses such as cell proliferation, migration, differentiation and apoptosis. Their actions are mediated by binding to the G-proteincoupled endothelial differentiation gene (Edg) receptor subfamily, referred to as S1P1-5 and LPA1-5, and regulate a variety of signalling pathways involved in numerous physiological processes and pathological conditions. Their importance during embryogenesis has been demonstrated by the generation of knock-out mice and specific roles have been assigned to these receptors. However, potential functional redundancy and the lethality of some mutants have complicated functional analysis in these models. Here we report the cloning of the S1P and LPA receptors in Xenopus laevis and tropicalis. Phylogenetic analyses demonstrate the high level of conservation of these receptors between amphibian and other vertebrate species. We have conducted a comparative expression analysis of these receptors during development and in the adult frog, by both RT-PCR and whole mount in situ hybridisation. In particular, we show that S1P1, 2 and 5 display distinct embryonic specific expression patterns, suggesting potentially different developmental roles for these receptors, and therefore for their ligands, during amphibian embryogenesis.

An essential role for LPA signalling in telencephalon development

“…Either LPAR6 is not an effector of FGF signalling in these processes, or different LPA receptor subtypes can compensate for defective LPAR6 signalling. Transcripts for lpar1, lpar2, lpar4 and lpar5 have been detected in Xenopus embryos (Lloyd et al, 2005;Massé et al, 2010a). As different LPA receptor subtypes have been shown to activate similar intracellular signalling pathways within a single cell (Dubin et al, 2010), it is possible that one or more of these Xenopus receptors could compensate for defective LPAR6 function at this stage.…”

“…This is only the second LPAR receptor, after LPAR1 (Estivill-Torrús et al, 2008), that has been shown to have a role in early neural development, even though multiple receptor subtypes are expressed in the developing nervous system (Ohuchi et al, 2008;Massé et al, 2010a). The cellular and molecular basis of this role will require further studies, as will identifying the source of the LPA signals.…”

“…LPA receptors are widely expressed in vertebrate embryos, with distinct but overlapping expression patterns (Ohuchi et al, 2008;Massé et al, 2010a). Several LPA receptors are expressed in the developing nervous system (Ohuchi et al, 2008) but loss-of-function studies have provided few clues as to their role in neural development.…”

Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development

“…Autotaxin is a lysophospholipase D that can bind to cell surface integrin and it catalyzes the hydrolysis of LPC to LPA. LPA binds to Edg and nonEdg receptors at the cell surface to stimulate PLCβ and other pathways (Massé et al, 2010). However, while present in the oocyte, LPA receptors are lost during oocyte maturation to the Xenopus egg but LPA may have an intracellular role.…”

Floralozone Ameliorated Atherosclerosis in Experimental Atherosclerotic Rats Involved with Sphingosine 1-Phosphate 1 Enhancement

“…S1P receptors are widely expressed in different tissues, so the S1P receptor family regulates many physiological processes and participates in various physiological functions, such as angiogenesis, neurogenesis, myelination, wound healing, and cholester- ol metabolism [27,28]. Therefore, the S1P receptor has become a target for the development of new drugs for AS [29,30]. In this study, we determined that the S1P1 receptor might be involved with Floralozone effect on AS.…”