Last update 01 Nov 2024

LPAR3

Last update 01 Nov 2024

Basic Info

Synonyms

Edg-7, EDG7, endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 7

+ [9]

Introduction

Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins.

Drugs associated with LPAR3

Ki-16198

Target

LPAR1 x LPAR3

Mechanism

LPAR1 antagonists [+1]

Active Org.-

Originator Org.

Kirin Brewery Co. Ltd.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

VPC12249

Target

LPAR1 x LPAR3

Mechanism

LPAR1 antagonists [+1]

Active Org.-

Originator Org.

University of Virginia

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LPAR3

100 Translational Medicine associated with LPAR3

0 Patents (Medical) associated with LPAR3

541

Literatures (Medical) associated with LPAR3

01 Oct 2024·The Plant Journal

The genetic basis of leaf hair development in upland cotton (Gossypium hirsutum)

Article

Author: Liu, Fang ; Hu, Daowu ; Fu, Guoyong ; Du, Xiongming ; Gao, Xu ; Tian, Yuan ; Wang, Jingjing ; Nazir, Mian Faisal ; Wang, Xiaoyang ; Peng, Zhen ; Xing, Aishuang ; Chen, Baojun ; Li, Hongge ; Tian, Chunyan ; Ma, Xinli ; Dai, Panhong ; Rong, Junkang ; Wang, Zhenzhen ; He, Shoupu

SUMMARYTrichomes, which originate from the epidermal cell of aerial organs, provide plants with defense and secretion functions. Although numerous genes have been implicated in trichome development, the molecular mechanisms underlying trichome cell formation in plants remain incompletely understood. Here, we using genome‐wide association study (GWAS) across 1037 diverse accessions in upland cotton (Gossypium hirsutum) to identify three loci associated with leaf pubescence (hair) amount, located on chromosome A06 (LPA1), A08 (LPA2) and A11 (LPA3), respectively. GhHD1, a previously characterized candidate gene, was identified on LPA1 and encodes an HD‐Zip transcription factor. For LPA2 and LPA3, we identified two candidate genes, GhGIR1 and GhGIR2, both encoding proteins with WD40 and RING domains that act as inhibitors of leaf hair formation. Expression analysis revealed that GhHD1 was predominantly expressed in hairy accessions, whereas GhGIR1 and GhGIR2 were expressed in hairless accessions. Silencing GhHD1 or overexpressing GhGIR1 in hairy accessions induced in a hairless phenotype, whereas silencing GhGIR2 in hairless accessions resulted in a hairy phenotype. We also demonstrated that GhHD1 interact with both GhGIR1 and GhGIR2, and GhGIR1 can interact with GhGIR2. Further investigation indicated that GhHD1 functions as a transcriptional activator, binding to the promoters of the GhGIR1 and GhGIR2 to active their expression, whereas GhGIR1 and GhGIR2 can suppress the transcriptional activation of GhHD1. Our findings shed light on the intricate regulatory network involving GhHD1, GhGIR1 and GhGIR2 in the initiation and development of plant epidermal hairs in cotton.

01 Oct 2024·Brain, Behavior, and Immunity

LPA3 agonist-producing Bacillus velezensis ADS024 is efficacious in multiple neuroinflammatory disease models

Article

Author: Hill, Colin ; Dixit, Bharat ; Acton, Susan ; Eishingdrelo, Haifeng ; Paul Ross, R ; Periyasamy, Kalaichitra ; Chesnel, Laurent ; O'Donnell, Michelle M

Neuroinflammation is a common component of neurological disorders. In the gut-brain-immune axis, bacteria and their metabolites are now thought to play a role in the modulation of the nervous and immune systems which may impact neuroinflammation. In this respect, commensal bacteria of humans have recently been shown to produce metabolites that mimic endogenous G-protein coupled receptor (GPCR) ligands. To date, it has not been established whether plant commensal bacteria, which may be ingested by animals including humans, can impact the gut-brain-immune axis via GPCR agonism. We screened an isopropanol (IPA) extract of the plant commensal Bacillus velezensis ADS024, a non-engrafting live biotherapeutic product (LBP) with anti-inflammatory properties isolated from human feces, against a panel of 168 GPCRs and identified strong agonism of the lysophosphatidic acid (LPA) receptor LPA3. The ADS024 IPA extracted material (ADS024-IPA) did not agonize LPA2, and only very weakly agonized LPA1. The agonism of LPA3 was inhibited by the reversible LPA1/3 antagonist Ki16425. ADS024-IPA signaled downstream of LPA3 through G-protein-induced calcium release, recruitment of β-arrestin, and recruitment of the neurodegeneration-associated proteins 14-3-3γ, ε and ζ but did not recruit the β βisoform. Since LPA3 agonism was previously indirectly implicated in the reduction of pathology in models of Parkinson's disease (PD) and multiple sclerosis (MS) by use of the nonselective antagonist Ki16425, and since we identified an LPA3-specific agonist within ADS024, we sought to examine whether LPA3 might indeed be part of a broad underlying mechanism to control neuroinflammation. We tested oral treatment of ADS024 in multiple models of neuroinflammatory diseases using three models of PD, two models of MS, and a model each of amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and chemo-induced peripheral neuropathy (CIPN). ADS024 treatment improved model-specific functional effects including improvements in motor movement, breathing and swallowing, and allodynia suggesting that ADS024 treatment impacted a universal underlying neuroinflammatory mechanism regardless of the initiating cause of disease. We used the MOG-EAE mouse model to examine early events after disease initiation and found that ADS024 attenuated the increase in circulating lymphocytes and changes in neutrophil subtypes, and ADS024 attenuated the early loss of cell-surface LPA3 receptor expression on circulating white blood cells. ADS024 efficacy was partially inhibited by Ki16425 in vivo suggesting LPA3 may be part of its mechanism. Altogether, these data suggest that ADS024 and its LPA3 agonism activity should be investigated further as a possible treatment for diseases with a neuroinflammatory component.

01 Sep 2024·Development & reproduction

Autotaxin Expression in the Uterus of Cycling Rats.

Article

Author: Kim, Hye-Soo ; Lee, Sung-Ho

Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP 2), is an enzyme with lysophospholipase D activity that converts lysophosphatidylcholine into lysophosphatidic acid (LPA). One of the LPA receptors, LPA3, is positively and negatively regulated by progesterone and estrogen, respectively. Furthermore, ATX expression in the rat uterus could be under the control of estrous cycle. In the present study, we used young normal cycling rats for further assess the uterine ATX expression and localization by reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. In the RT-PCR study, ATX mRNA level at Metestrus (1.00±0.026 AU) was significantly higher than that at Proestrus (0.42±0.046 AU, p<0.001) and the level at Diestrus (0.75±0.107 AU, p<0.05) was significantly higher than that at Proestrus. Among the luminal epithelial cells, the order of the ATX signal intensities was Metestrus>Diestrus>Proestrus>Estrus. Among the myometrial cells, the order of the signal intensities was Diestrus>Proestrus>Estrus>Metestrus. Among the glandular epithelial cells, the order of the signal intensities was Proestrus>Estrus=Metestrus= Estrus. The present study indicates that expression and localization of uterine ATX may be under the control of sex steroids during the estrous cycle. Further studies on the ATX signaling-sex steroid relationship will be providing better understanding on in normal and pathophysiological state of uterus.

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LPAR3

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