Functional analysis of mammalian CRY protein in photo-reception

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14646
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: University of Tsukuba
• Principal Investigator: Tsubota Arisa (平野有沙) 筑波大学, 医学医療系, 助教 (60806230)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 概日時計 / 概日リズム / CRY

Outline of Final Research Achievements

Non-visual photo-reception contributes to resetting of the circadian clock. In the modern society, the circadian disorder recognized as misalignment of body clock and environmental cycle is a serious issue. In mammals, OPN4 is known as a circadian photo-receptor, while it is still unknown whether a putative photoreceptor, CRY, functions in circadian light-resetting. To investigate the function of CRY in photo-entrainment, we generated retina-specific Cry1 conditional knockout mice. The mice showed free-running even in light-dark cycle. Jet lag experiment did not affect the free-running activity in the knockout mice, while control mice showed re-entrainment to new light-dark schedule. We also examined the effect of CRY on photo activation of OPN4 in cell culture. The expression of Cry1 increased Gq signaling mediated by OPN4. Knockdown of Cry1 and Cry2 decreased the activity of OPN4, suggesting that CRY has functional interaction of OPN4 and contributed to light-sensing.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

概日時計は約1日周期の概日リズムを生み出す原動力である。24時間型社会と呼ばれる現代社会では夜間においても強い光に曝露され、体内リズムと外界の明暗サイクルとの間にズレが生じやすい。概日リズム障害の治療として光療法は安全かつ簡便で、極めて有効なツールである。そのため、概日時計に入力する光応答機構を理解することは概日リズム障害の発症機序の解明とその解決に不可欠であるが、視覚情報を伴わない非視覚光受容の分子的な理解は遅れている。本研究は、哺乳類において新たにCRYタンパク質が非視覚光受容に必須であることを示し、その分子メカニズムに迫ったものであり、概日リズム障害の治療という観点でも極めて重要である。