Regulation of microtubule function and control of endocrine mechanism by tubulin acetylation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K18982
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Teikyo University
• Principal Investigator: Nakakura Takashi 帝京大学, 医学部, 講師 (60568658)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 微小管 / αチューブリン / アセチル化修飾 / 下垂体 / ACTH細胞 / グルココルチコイド受容体 / ATAT1 / 核移行

Outline of Final Research Achievements

Microtubules are tubular structures constructed by α- and β-tubulin, and are not only distributed in the cytoplasm as a cytoskeleton, but also play an important role as a delivery rail for intracellular transport. The lysine residue at the 40th amino acid sequence of α-tubulin faces the liminal side of microtubule and is acetylated by α-tubulin N-acetyltransferase 1 (ATAT1). However, the role of tubulin acetylation in the endocrine cells of the pituitary was unknown. In this study, we examined a cell biological analysis using the mouse pituitary corticotrophs cell line AtT20. These results indicated that the gene expression of ATAT1 was regulated by hormones and the tubulin acetylation induced by ATAT1 promotes the nuclear translocation of glucocorticoid receptor. We conclude that ATAT1 finely tunes the cellular responses of corticotrophs to hormonal stimulation through an intracellular feedback circuit.

Free Research Field

内分泌形態学

Academic Significance and Societal Importance of the Research Achievements

本研究を遂行することで、αチューブリンアセチル化修飾の内分泌細胞における新しい役割を明らかにできた。チューブリンのアセチル化修飾は神経細胞やがん細胞を含む多種多様な細胞で確認されているが、内分泌細胞での機能を明らかにしたのは本研究が初となる。今後、分子レベルで作用点を明らかにすることができれば、内分泌調節における新しい細胞応答モデルの提唱につながる。さらに、本研究の成功によって、将来的に修飾そのものや修飾酵素を標的とした新しい治療薬の開発および病態に対する治療戦略の確立につながる可能性もあることから、本研究による社会的貢献度は高い。