Comprehensive analysis of the sphingolipid recycling pathway based on genome-wide screening

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02435
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: YAMAJI Toshiyuki 国立感染症研究所, 細胞化学部, 室長 (50332309)
• Co-Investigator(Kenkyū-buntansha): 谷田 以誠 順天堂大学, 医学部, 先任准教授 (30296868)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: スフィンゴ脂質 / サルベージ経路 / CRISPRライブラリー / ゲノムワイド探索 / リソソーム / 血清

Outline of Final Research Achievements

We established cells that express glycolipids in a serum sphingolipid-dependent manner, i.e., the sphingolipid recycling metabolic pathway can be easily traced, and identified genes involved in the recycling pathway comprehensively by a genome-wide CRISPR KO screen using these cells. Lipid analysis using KO cell lines of the identified genes revealed strong contributions to the salvage pathway, especially in the LDL receptor, acid sphingomyelinase (SMPD1), and sphingosine monophosphate phosphatase (SGPP1). Several factors involved in intracellular trafficking, including NPC1, were also found to contribute to the salvage pathway, although to a lesser extent than the above factors.

Free Research Field

糖鎖生物学　脂質生物学　感染症学

Academic Significance and Societal Importance of the Research Achievements

本研究はスフィンゴ脂質代謝の基礎研究のみならず、リソソームの細胞生物学的研究及びリソソーム病（脂質蓄積症）解析等、より広い研究分野において重要な知見をもたらす。さらにスフィンゴ脂質の代謝バランスは糖尿病等の生活習慣病に影響を及ぼすことから、本研究における血清由来スフィンゴ脂質の代謝機構解明が、これらの疾患に対してスフィンゴ脂質制御による治療を考える上での有用な知見をもたらすものと期待する。