Novel lysophosphoplipid receptors: their structure and function

Abstract

This article is available online at http://www.jlr.org with plasma concentrations of 10-30 nM and several hundred nanomoles, respectively ( 3, 4 ). Both LPA and S1P have critical roles in multiple cellular events through G protein-coupled receptors (GPCRs). Six GPCRs have been identifi ed for LPA (LPA 1-6 ) and fi ve GPCRs have been identifi ed for S1P (S1P 1-5 ) ( 5 ), and nomenclature of these LysoGPs receptors has recently been proposed by Kihara et al. ( 6 ). These receptors are grouped into two classes, the Edg and P2Y families, respectively. LPA 1-3 and all fi ve of the S1P receptors, S1P [1][2][3][4][5] , are members of the Edg family, while LPA 4-6 are members of the P2Y family. In addition, LPA is an endogenous ligand for PPAR ␥ ( 7 ), and was shown to activate transient receptor potential cation channel subfamily V member 1 (TRPV1) channels leading to an infl ux of Ca 2+ ions through TRPV1 ( 8 ). Studies on gene-targeted mice and human genetic diseases have clearly shown that each receptor has specifi c roles in both physiological and pathological conditions. For example, LPA has a pivotal role in neurogenesis ( 9 ) and has also been implicated in the development of lung fi brosis ( 10 ) via LPA 1 . LPA exhibits unique roles in implantation of fertilized eggs via LPA 3 ( 11 ) and hair follicle formation via LPA 6 ( 12 ). LPA is produced by at least two pathways where multiple phospholipase activities are involved ( 3 ). Lysophospholipase D/autotaxin/NPP2 produces LPA from LysoGPs such as LPC, while phosphatidic acid (PA)-selective PLA 1 ␣ (PA-PLA 1 ␣ ) and PA-PLA 1 ␤ produce LPA from PA by their PLA 1 activities. In contrast, S1P is produced intracellularly by phosphorylation Abstract It is now accepted that lysophospholipids (LysoGPs) have a wide variety of functions as lipid mediators that are exerted through G protein-coupled receptors (GPCRs) specifi c to each lysophospholipid. While the roles of some LysoGPs, such as lysophosphatidic acid and sphingosine 1-phosphate, have been thoroughly examined, little is known about the roles of several other LysoGPs, such as lysophosphatidylserine (LysoPS), lysophosphatidylthreonine, lysophosphatidylethanolamine, lysophosphatidylinositol (LPI), and lysophosphatidylglycerol. Recently, a GPCR was found for LPI (GPR55) and three GPCRs (GPR34/LPS 1 , P2Y10/ LPS 2 , and GPR174/LPS 3 ) were found for LysoPS. In this review, we focus on these newly identifi ed GPCRs and summarize the actions of LysoPS and LPI as lipid mediators.

A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development

“…Whilst the ions at m/z 498, 507, and 509 are yet to be identified, they fall into the mass range of lysoPLs, DGs and sterol lipids, all of which are involved in regulatory processes. Indeed, these hormone-like molecules are now the focus of many research groups, due to the increasing identification of their receptors and thus knowledge of their regulatory pathways(Fuchs et al 2012, Makide et al 2014). For example, LPA has been shown to mediate fibroblast migration and recruitment as well as increasing vascular permeability in a bleomycin mouse model of fibrosis, highlighting the impact these small molecular weight lipids have on disease progression(Tager et al 2008).…”

Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates

“…LPEs belong to a large and diverse class of deacylated phospholipids, called lysophospholipids, that include structural components of cellular membranes as well as biologically active lipid mediators (46,47). Although LPEs are found in most bacterial and eukaryotic cell membranes and present in somewhat elevated concentrations in many marine and estuarine bacteria (48), little is known about how and in what contexts LPEs might act as signaling molecules (47,49).…”

“…Although LPEs are found in most bacterial and eukaryotic cell membranes and present in somewhat elevated concentrations in many marine and estuarine bacteria (48), little is known about how and in what contexts LPEs might act as signaling molecules (47,49).…”

Biogenesis, transport and remodeling of lysophospholipids in Gram-negative bacteria

“…Inflamed tissues secrete LPLs as potent chemotactic molecules (7,8) or stimulating factors (9), which are considered as potential biomarkers of certain diseases (10,11). Lysophosphatidic acid (LPA) and sphingosine-1-phosphate are potent signaling messengers and mitogens (12). Lysophosphatidylcholine (LPC) is a lipid precursor for biogenesis of docosahexaenoic acid, a primary structural component of the human brain, cerebral cortex and retina (13).…”