Characterization of an intellectual disability-related secretory ligand, LGI3, and identification of its receptor proteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16269
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: MIYAZAKI Yuri 生理学研究所, 分子細胞生理研究領域, 特任助教 (70837260)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 知的障害 / 脳神経疾患 / LGI3 / 分泌蛋白質

Outline of Final Research Achievements

Dysfunction of LGI family proteins (LGI1-4) causes various neurological disorders. However, the physiological functions of LGI3 remain unclear. Recently, the association between human LGI3 gene mutations and intellectual disability was reported, suggesting that LGI3 is essential for normal brain activity. In this study, we investigated the physiological functions of LGI3 and the mechanisms by which LGI3 dysfunction causes brain abnormalities. We determined the widespread localization of LGI3 protein in the brain and also comprehensively identified the LGI3-interacting proteins including its receptor candidates by proteomics analysis. These results provide useful information to understand the (patho-)physiological functions of LGI3 in the brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

LGI3遺伝子変異と知的障害発症との関連性から、LGI3タンパク質の生理的な役割を明らかにすることは大変重要である。本研究で得られたLGI3の詳細な脳内局在や結合タンパク質等の情報は、その機能を理解するための有用な知見であり、LGI3の機能不全が引き起こす病態を明らかにするための基礎となる研究成果である。また、ファミリータンパク質LGI1の受容体であるADAM22遺伝子変異と知的障害を含む重度の脳症発症との関連性についても研究を行い、ADAM22遺伝子変異が様々な機序でタンパク質機能不全を引き起こし、疾患発症に寄与する可能性を報告した。