Analysis of synaptic connectivity regulated by Sparcl1/Hevin variants during brain development(Fostering Joint International Research)

2019 Fiscal Year Final Research Report

• Project/Area Number: 16KK0158
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: University of Tsukuba
• Principal Investigator: TSURUTA Fuminori 筑波大学, 生命環境系, 助教 (30571450)
• Project Period (FY): 2017 – 2019
• Keywords: Sparcl1/Hevin / USP15 / neurons / astrocytes / microglia

Outline of Final Research Achievements

RNA metabolism is regulated in timing- and region-specific manners. Recently, it has been reported that a defect in this process leads to developmental disorders. So far, we have found that loss of USP15 causes an abnormal spliceosomal function, leading to global splicing errors. In this study, we have focused on the Sparcl1 mutant produced by USP15 deficient brain and analyzed a link between Sparcl1 abnormality and ER stress. Since USP15 and Sparcl1 act as responsible genes for autism, we expect that our data provide a clue for understanding that underlie not only RNA metabolism but also developmental disorders.

Free Research Field

神経科学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本課題で検証を行ったUSP15とSparcl1は、双方とも自閉症の責任遺伝子として報告されている。その一方で、これら遺伝子の異常がなぜ自閉症につながるのか明らかではなかった。本研究課題では、これら遺伝子の異常が、小胞体ストレスの誘導につながることを新たに発見した。小胞体ストレスと発達障害の関連はほとんど解析が進んでいないことから、本研究成果は、発達障害研究に対する新しい視点を提供できるのではないかと期待している。