Molecular characterization of GPR84 in domestic cats

Ichiro Yamamoto; Masaki Michishita; Koki Fujita; Tamami Sakai; Noriyasu Sasaki; Koh Kawasumi

doi:10.1016/j.ygcen.2024.114520

Molecular characterization of GPR84 in domestic cats

Gen Comp Endocrinol. 2024 Jul 1:353:114520. doi: 10.1016/j.ygcen.2024.114520. Epub 2024 Apr 18.

Authors

Ichiro Yamamoto¹, Masaki Michishita², Koki Fujita³, Tamami Sakai³, Noriyasu Sasaki³, Koh Kawasumi³

Affiliations

¹ Department of Veterinary Biochemistry, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan. Electronic address: ichiroy@nvlu.ac.jp.
² Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan.
³ Department of Veterinary Biochemistry, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan.

PMID: 38641150
DOI: 10.1016/j.ygcen.2024.114520

Abstract

G protein-coupled receptor 84 (GPR84) was cloned as an orphan receptor, and medium-chain fatty acids were then revealed as endogenous ligands. GPR84 is expressed in immune cells and is believed to protect liver function from lipotoxicity caused by overeating and high-fat diet intake. This study aimed to present the molecular characterization of GPR84 in domestic cats. The deduced amino acid sequence of the feline GPR84 shows high sequence homology (83-89 %) with the orthologues from other mammalians by cDNA cloning of feline GPR84. Remarkably high mRNA expression was observed in the bone marrow by Q-PCR analysis. The inhibition of intracellular cAMP concentration was observed in cells transfected with feline GPR84 and treated with medium-chain fatty acids. Immunostaining of GPR84 and free fatty acid receptor 2 (FFAR2)/GPR43 in the bone marrow, where high mRNA expression was observed, showed reactions in macrophages and myeloid cells. To clarify whether the receptor formed homo/hetero-merization, GPR84 and FFARs were analyzed using Nano-Luc binary technology and NanoLuc bioluminescence resonance energy transfer technologies, which revealed that GPR84 formed more heteromers with FFAR2 than homomers with each other. In addition, when GPR84 and FFAR2/GPR43 were cotransfected in the cell, their localization on the cell membrane was reduced compared with that when single receptors were transfected. These results indicated that GPR84 is a functional receptor protein that is expressed in cat tissues and may have a protein-protein interaction with FFAR2/GPR43 on the cell membrane.

Keywords: Cat; Free fatty acid receptor 2; G protein-coupled receptor 84; GPR43; cAMP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cats
Receptors, G-Protein-Coupled* / genetics
Receptors, G-Protein-Coupled* / metabolism

Substances

Receptors, G-Protein-Coupled