Lysophospholipid receptor nomenclature review: IUPHAR Review 8

Abstract

Lysophospholipids encompass a diverse range of small, membrane-derived phospholipids that act as extracellular signals. The signalling properties are mediated by 7-transmembrane GPCRs, constituent members of which have continued to be identified after their initial discovery in the mid-1990s. Here we briefly review this class of receptors, with a particular emphasis on their protein and gene nomenclatures that reflect their cognate ligands. There are six lysophospholipid receptors that interact with lysophosphatidic acid (LPA): protein names LPA1 - LPA6 and italicized gene names LPAR1-LPAR6 (human) and Lpar1-Lpar6 (non-human). There are five sphingosine 1-phosphate (S1P) receptors: protein names S1P1 -S1P5 and italicized gene names S1PR1-S1PR5 (human) and S1pr1-S1pr5 (non-human). Recent additions to the lysophospholipid receptor family have resulted in the proposed names for a lysophosphatidyl inositol (LPI) receptor - protein name LPI1 and gene name LPIR1 (human) and Lpir1 (non-human) - and three lysophosphatidyl serine receptors - protein names LyPS1 , LyPS2 , LyPS3 and gene names LYPSR1-LYPSR3 (human) and Lypsr1-Lypsr3 (non-human) along with a variant form that does not appear to exist in humans that is provisionally named LyPS2L . This nomenclature incorporates previous recommendations from the International Union of Basic and Clinical Pharmacology, the Human Genome Organization, the Gene Nomenclature Committee, and the Mouse Genome Informatix.

Keywords: FTY720 (fingolimod); G protein-coupled receptors; lipid mediators; lysophospholipids; molecular pharamacology.

Figure 1

Lysophospholipid receptors and their intracellular signalling pathways. Lysophospholipid ligands (LPA, S1P, LPI and LysoPS) bind to their specific GPCRs, which activate heterotrimeric G-proteins (defined here by their α subunits) to initiate downstream signalling cascades. R in the chemical structures is a variable acyl side chain.

Figure 2

Phylogenetic tree of related GPCRs and amino acid sequence identities. (A) A molecular phylogenetic tree of human GPCRs. The selected GPCR protein sequences were analysed for the phylogenetic reconstruction by the ‘All against All’ sequence programme at the Computational Biochemistry Research Group server of the ETH Zürich. (B) Pair-wise matrices comparing amino acid sequences of lysophospholipid receptors. The upper and lower matrices specify identities among lysophospholipid receptors in human and mouse respectively. The amino acid sequence identities are shown in a gray-to-white gradient. The numbers in the boxes were calculated by Clustal Omega (Sievers et al., 2011).