Functional roles of novel S-palmitoylation on beta 3-adrenergic receptor

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18988
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kobe University
• Principal Investigator: Adachi Naoko 神戸大学, バイオシグナル総合研究センター, 助教 (70604510)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: パルミトイル化 / ベータ３アドレナリン受容体 / GPCR

Outline of Final Research Achievements

Palmitoylation is a reversible lipid modification contributing to the regulation of G-protein coupled receptor (GPCR) function. Despite its importance, palmitoylation status of the β3-adrenergic receptor (β3AR), a GPCR critical for lipid metabolism and thermogenesis, has never been determined. We report here that human β3AR is palmitoylated on four cysteine residues at sites in second and third intracellular loop and at two sites in the C-terminal tail. Palmitoylation deficient mutant exhibited lowered cAMP production and ERK1/2 phosphorylation upon agonist stimulation indicating importance for downstream signaling. In addition, less palmitoylated receptor showed altered half-life. These results suggesting that multiple palmitoylations of human β3AR regulate receptor functions.

Free Research Field

分子薬理学