Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an extracellular signaling molecule by binding to and activating at least five known G protein-coupled receptors (GPCRs): LPA(1)-LPA(5). They are encoded by distinct genes named LPAR1-LPAR5 in humans and Lpar1-Lpar5 in mice. The biological roles of LPA are diverse and include developmental, physiological, and pathophysiological effects. This diversity is mediated by broad and overlapping expression patterns and multiple downstream signaling pathways activated by cognate LPA receptors. Studies using cloned receptors and genetic knockout mice have been instrumental in uncovering the significance of this signaling system, notably involving basic cellular processes as well as multiple organ systems such as the nervous system. This has further provided valuable proof-of-concept data to support LPA receptors and LPA metabolic enzymes as targets for the treatment of medically important diseases that include neuropsychiatric disorders, neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis, and cancer.

https://www.scripps.edu/chun/PDFs/Choi%20Ann%20Rev%20Pharmacol%20Toxicol%202010.pdf

LPA Receptors: Subtypes and Biological Actions

LPA Receptor Signaling: Pharmacology, Physiology, and Pathophysiology

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.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.12678

Lysophospholipid receptor nomenclature review: IUPHAR Review 8

Regulation and biological activities of the autotaxin-LPA axis

Lysophosphatidic Acid Signaling in the Nervous System

In order to explore a possibility that the cricket Gryllus bimaculatus would be a useful model to unveil molecular mechanisms of human diseases, we performed loss-of-function analyses of Gryllus genes homologous to human genes that are responsible for human disorders, fragile X mental retardation 1 (fmr1) and Dopamine receptor (DopR). We cloned cDNAs of their Gryllus homologues, Gb'fmr1, Gb'DopRI, and Gb'DopRII, and analyzed their functions with use of nymphal RNA interference (RNAi). For Gb'fmr1, three major phenotypes were observed: (1) abnormal wing postures, (2) abnormal calling song, and (3) loss of the circadian locomotor rhythm, while for Gb'DopRI, defects of wing posture and morphology were found. These results indicate that the cricket has the potential to become a novel model system to explore human neuronal pathogenic mechanisms and to screen therapeutic drugs by RNAi.

Loss‐of‐function analyses of the fragile X‐related and dopamine receptor genes by RNA interference in the cricket Gryllus bimaculatus

Lysophospholipids (LPs) such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are known to mediate various biological responses, including cell proliferation, migration, and differentiation. To better understand the role of these lipids in mammalian early development, we applied whole-mount in situ hybridization techniques to E8.5 to E12.5 mouse embryos. We determined the expression patterns of the following LP receptor genes, which belong to the G protein–coupled receptor (GPCR) family: EDG1 to EDG8 (S1P1 to S1P5 and LPA1 to LPA3), LPA4 (GPR23 /P2Y9), and LPA5 (GPR92). We found that the S1P/LPA receptor genes exhibit overlapping expression patterns in a variety of organ primordia, including the developing brain and cardiovascular system, presomitic mesoderm and somites, branchial arches, and limb buds. These results suggest that multiple receptor systems for LPA/S1P lysophospholipids may be functioning during organogenesis. Developmental Dynamics 237:3280–3294, 2008. © 2008 Wiley-Liss, Inc.

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.21736

Expression patterns of the lysophospholipid receptor genes during mouse early development.

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Loss‐of‐function analyses of the fragile X‐related and dopamine receptor genes by RNA interference in the cricket Gryllus bimaculatus

Expression patterns of the lysophospholipid receptor genes during mouse early development.