2009 Fiscal Year Final Research Report

Role of LRP5 in various metabolic pathways

Research Project

Project/Area Number	19300227
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Applied health science
Research Institution	Tohoku University
Principal Investigator	YAMAMOTO Tokuo Tohoku University, 加齢医学研究所, 教授 (30192412)
Project Period (FY)	2007 – 2009
Keywords	生活習慣病 / コレステロール
Research Abstract	In previous studies, we showed that the deficiency of LRP5, an LDL receptor related protein, impairs various metabolic pathways including cholesterol, glucose and calcium. We also showed that the lack of LRP5 enhances the formation of atherosclerosis, using mice lacking both apoE and LRP5. To further clarify the role of LRP5 in these metabolic disorders, we purified various agonists and antagonists of LRP5, including Wnt proteins, Dickopf 1-3, soluble frizzled related proteins, soluble LRP5 and LRP6 lacking membrane domains. Purification of Wnt proteins without detergents was extremely difficult because they are modified with palmitate. Nusse and his colleges purified Wnt3a using Triton X-100 and CHAPS, showing that Wnts proteins are modified with palmitate, thereby exhibiting extremely hydrophobic character. In this study, I purified Wnt3a、 Wnt 5a and Wnt4 without using detergents and characterized. The purification and characterization of these proteins will be published.