Functional analysis of ABC proteins in primary cilia

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K05434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: NAGATA Koh 京都大学, 農学研究科, 研究員 (70401213)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 一次繊毛 / ABCタンパク質 / ABCA1 / ABCB4 / コレステロール

Outline of Final Research Achievements

Primary cilia are antenna-like organelles found on the surface of most mammalian cells, which sense the extracellular environment and convey signaling information to the cell. Membrane lipid composition and distribution are involved in the formation and function of primary cilia. However, its regulatory mechanism remains unclear. In the present study, we focused on ABC proteins which are involved in the membrane lipid dynamics. We found that the formation of primary cilia was suppressed in ABCA1 knockdown cells. We observed that cholesterol was enriched at the tip of cilium, and ABCB4 was localized on the ciliary membrane, sometimes at the tip of the cilium. Our results suggest the contribution of ABC proteins in the formation and function of primary cilia.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

一次繊毛の形成異常や機能不全は、網膜色素変性、多発性嚢胞腎、内臓逆位など多様な症状を呈する「繊毛病」を引き起こす。膜の脂質組成や分布は一次繊毛の形成や機能に関わるが、その制御機構については不明な点が多い。本研究において、ABCA1やABCB4などのABCタンパク質による時空間的な膜脂質制御が一次繊毛の形成や機能を調節する可能性が示唆されたことは、繊毛病の病因や病態の解明に寄与すると期待される。