Sato, K, Mogi, C, Mighell, AJ orcid.org/0000-0002-9624-6923 et al. (1 more author) (2020) A missense mutation of Leu74Pro of OGR1 found in familial amelogenesis imperfecta actually causes the loss of the pH-sensing mechanism. Biochemical and Biophysical Research Communications, 526 (4). pp. 920-926. ISSN 0006-291X
Abstract
Ovarian cancer G protein-coupled receptor 1 (OGR1), also known as GPR68, is a proton-sensing G protein-coupled receptor (GPCR) coupling to Gq/11/phospholipase C/Ca2+ signaling pathways. The specific histidine residues at the extracellular surface of OGR1 are suggested to be involved in the proton sensing. Later, some metal ions, including nickel ion (Ni2+), are also indicated to be OGR1 ligands. OGR1 polymorphic variants have recently been found in three families with amelogenesis imperfecta, which suggested that OGR1 is required for the process of dental enamel formation. One of these families possesses a missense mutation from leucine to proline at 74 (L74P) of OGR1. In the present study, we characterized HEK293 cells with L74P OGR1 (L74P-OGR1) and hemagglutinin (HA)-tag, as compared with cells with wild-type OGR1 (WT-OGR1) and HA-tag. We found that either acidic pH or NiCl2 induced intracellular Ca2+ mobilization and morphological change in WT-OGR1-transfected cells; however, the extracellular stimulus-induced actions were severely damaged in L74P-OGR1-transfected cells. We further confirmed that either WT-OGR1 or L74P-OGR1 is localized mainly in the surface of the cells, but only WT-OGR1 is internalized in response to acidification or NiCl2. Thus, the L74P-OGR1 protein may be distributed in the plasma membranes but severely damaged in the receptor functions. We speculate that L74P in the second transmembrane domain in OGR1 may result in conformational changes in the receptor, thereby disturbing the sensing extracellular signals, i.e., protons or metal ions, and/or transducing them to the intracellular signaling machinery through G proteins.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Elsevier Inc. All rights reserved. This is an author produced version of an article published in Biochemical and Biophysical Research Communications. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Extracellular acidification; G protein-coupled receptor; Intracellular Ca2+; Missense variant; OGR1 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Surgery (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Apr 2020 14:26 |
Last Modified: | 29 Jul 2022 12:56 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bbrc.2020.04.005 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:159875 |
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