Production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis

Table 1 Expression pattern of lysophosphatidic acid receptors and their known physiological functions in humans and mice

Name	Information	Previous orphan names	Major expression tissue (high to low level)	Knockout effects in mouse	Biological functions	Ref.
LPA1	Human chromosome locus 9q31.3; 41.1 kDa1; 364 aa2; Identity3 97.3%	vzg-1, edg-2, 39.4 kDa; 344 aa mrec1.3, lpA1	Brain, placenta, urinary bladder, uterus, testis, lung, small intestine, heart, stomach, kidney, spleen, thymus, and skeletal muscle.	Perinatal lethality, retarded growth, defective olfaction, reduced body size, craniofacial dysmorphism with blunted snouts, and increased apoptosis in sciatic nerve Schwann cells.	Neurodevelopment regulation, cell proliferation, differentiation, apoptosis and survival, cell-cell contact through serum-response element activation, cell migration and cytoskeletal organization, Ca2+ homeostasis, cAMP-regulated cellular processes and adenylyl cyclase inhibition	Yung et al[68], 2014; Archbold et al[138], 2014; Choi et al[139], 2008; Anliker et al[103], 2013; Sakai et al[104], 2013; Wittpoth et al[98], 1999; An et al[82], 1998; Contos et al[107], 2000; Contos et al[106], 2000; Fukushima et al[84], 2001.
	Mouse chromosome locus 4, 32.2 cM; 41.1 kDa; 364 aa		Brain, heart, lungs, stomach, intestine, placenta, kidneys, spleen, uterus, testes.
LPA2	Human chromosome 19p13.11; 39.1 kDa; 351 aa; Identity 83.5%	edg-4, lpA2	Leukocytes, testis, prostate, spleen, thymus and pancreas.	Normal	Cell migration, viable and healthy, nervous system development and immune system regulation.	Yung et al[68], 2014; An et al[82], 1998; Contos et al[106], 2000b; Archbold et al[138], 2014; Ohuchi et al[111], 2008; Choi et al[110], 2010; Valentine et al[140], 2008; Xu et al[113], 2004; Lai et al[112], 2005; Contos et al[115], 2002; Choi et al[139], 2008.
	Mouse chromosome 8, 33.91 cM; 38.7 kDa; 348 aa		Kidney, testis, uterus, lung, stomach, spleen, thymus, postnatal brain, and heart.
LPA3	Human chromosomal locus 1p22.3; 40.1 kDa; 353 aa; Identity 91.2%	edg-7, lpA3	Heart, testis, prostate, pancreas, lung, ovary, and brain.	Delayed embryo implantation, embryo crowding, and reduced litter size for female null mutants.	Male and female reproductive physiology, inflammation, cell Ca2+ homeostasis and cAMP regulation, vertebrate left-right patterning during embryogenesis.	Yung et al[68], 2014; Bandoh et al[83], 1999; Im et al[116], 2000; Contos et al[107], 2000a; Zhao et al[117], 2015; Ye et al[118], 2010; Hama et al[119], 2010; Lai et al[120], 2012
	Mouse chromosome locus 3, 71.03 cM; 40.3 kDa; 354 aa		Lung, kidney, uterus, testis, small intestine, brain, heart, stomach, placenta, spleen, and thymus.
LPA4	Human chromosome Xq21.1; 41.9 kDa; 370 aa; Identity 98.4%	P2Y9/GPR23	Ovaries, thymus, pancreas, brain, heart, small intestine, testis, prostate, colon, and spleen.	Inhibition of its differentiation into osteoblasts in human mesenchymal stem cell line; For mouse: increased trabecular bone volume, number, and thickness; pericardial effusions, severe edema and hemorrhage, abnormally dilated blood and lymphatic vessels and lymph sacs, and impaired pericyte recruitment.	ROCK-dependent cell aggregation and N-cadherin-dependent cell adhesion, cAMP accumulation, differentiation of immortalized hippocampal progenitor cells, negatively cell motility regulation and osteogenesis.	Yung et al[68], 2014; Ohuchi et al[111], 2008; Choi et al[110], 2010; Liu et al[123], 2010; Mansell et al[124], 2010; Liu et al[125], 2009; Sumida et al[126], 2010; Yanagida et al[71]; Lee et al[97], 2007; Rhee et al[121], 2006; Lee et al[122], 2008
	Mouse chromosome X region D; 41.9 kDa; 370 aa		Heart, ovary, skin, thymus, and bone Marrow.
LPA5	Human chromosome 12p13.31; 41.3 kDa; 372 aa; Identity 79.0%	GPR92	Spleen, heart, small intestine, placenta, colon, and liver.	Reduced lung metastasis by melanoma cells.	Neurite retraction, stress fiber formation, receptor internalization, water absorption, Ca2+ mobilization and cAMP accumulation, LPA-induced release of chemokine ligand 4 in mast cells.	Yung et al[68], 2014; Lee et al[87], 2006; Lee et al[141], 2015; Amisten et al[142], 2008; Lundequist et al[129], 2011; Araki et al[130], 2014; Lin et al[128], 2010; Yanagida et al[143], 2013
	Mouse chromosome 6, 59.21 cM; 41.4 kDa; 372 aa		Small intestine, lung, heart, stomach, colon, spleen, thymus, skin, liver, platelets, mast cells, gastrointestinal lymphocytes, and dorsal root ganglia.
LPA6	Human chromosome 13q14.2; 39.4 kDa; 344 aa; Identity 93.0%	P2Y5	Hair, skin.	Hypotrichosis	Hair development, increased intracellular Ca2+, reduced forskolin-stimulated cAMP accumulation, and ERK1/2 activation	Yanagida et al[144], 2011; Yanagida et al[143], 2013; Raza et al[135], 2014; Dong et al[145], 2014; Lee et al[141], 2015; Lee et al[133], 2009
	Mouse chromosome 14, region D3; 39.4 kDa; 344 aa		Hair, immune cells.

¹Molecular mass were obtained from UniProt[146];

²aa means amino acids;

³Identities between human and mouse lysophospholipid receptors were calculated in UniProt[146]. vzg-1: Ventricular zone gene-1; edg: Endothelial differentiation gene.