Activation mechanism of photoreceptor protein OPN4 and its physiological meaning

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16085
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Waseda University (2022); The University of Tokyo (2019-2021)
• Principal Investigator: Kimata Naoki 早稲田大学, 理工学術院, 助教 (40822929)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: メラノプシン / 非視覚光応答 / GPCR

Outline of Final Research Achievements

Melanopsin is a rhodopsin-like photoreceptor protein which regulates non-image forming (NIF) functions in mammals. The purpose of this project is to elucidate importance of the molecular properties of melanopsin for regulation of the NIF functions. First, I analyzed some mutants of melanopsin which are expected to change activation efficiency or specificity of G protein activation, respectively. The results were that these mutants showed different photoresponses from originally predicted, which means that melanopsin does not have the same activation mechanism as those of rhodopsin. In addition, to evaluate the functions of molecular properties of melanopsin on NIF responses in vivo, I generated the mice expressing recombinant melanopsin instead of native one. These mice showed similar NIF response to wildtype mice, meaning that experiment system for testing the effect of melanopsin molecular properties on the physiological NIF functions is established.

Free Research Field

光生物学

Academic Significance and Societal Importance of the Research Achievements

本成果の学術的意義として、光受容体の分子としての機能が個体の生理機能と関連している可能性を見出した点にある。従来、メラノプシンとロドプシンは活性化メカニズムが類似していると考えられていたが、本成果によって生物は生理機能に応じて活性化メカニズムの異なる光受容体を使い分けていることが示唆された。また、組換えメラノプシンを生体に発現・機能させた成果は、将来的にはメラノプシン由来の体の不調、例えば季節性情動障害などの対処法の発見につながる可能性が考えられる。