Functional deorphaning of novel phospholipases

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390021
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MURAKAMI Makoto 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 参事研究員 (60276607)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 酵素 / 脂質 / 生体分子 / 遺伝子 / 組織・細胞 / 遺伝子改変マウス / リピドミクス / 病態

Outline of Final Research Achievements

Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze the sn-2 position of phospholipids to generate fatty acids and lysophospholipids. Mammalian genomes encode genes for more than 30 PLA2s or related enzymes, which are subdivided into several groups on the basis of their structures and enzymatic properties. In this study, we analyzed knockout mice for several PLA2s whose functions had been unknown to reveal their pathophysiological roles. We provide evidence that (1) sPLA2-IIE regulates metabolism by hydrolyzing lipoprotein phospholipids, (2) sPLA2-XIIA regulates mast cell activation and acquired immunity, (3) PNPLA7 controls hepatic choline homeostasis and thereby systemic metabolism, and (4) PNPLA1 regulates epidermal ceramide metabolism and associated skin barrier function.

Free Research Field

脂質生物学