Understanding the anchoring disruptor or modulator of subunits of the exocyst provides a new therapeutic strategy for various diseases.

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K06815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Yamagata University
• Principal Investigator: Tanaka Toshiaki 山形大学, 医学部, 客員研究員 (70536987)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 開口分泌小胞 / 脱リン酸化

Outline of Final Research Achievements

Sec6 is one of the subunits of the exocyst, an evolutionarily conserved eight-protein complex comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7) and Exo84 (EXOC8) subunits. Recently, several researches have showed that Sec6 is associated with various cellular mechanisms such as neurite growth, cell adhesion, cell polarity, cell migration, cell cycle, NFκB signaling, and apoptosis. These functions may be dependent or independent on its basic role of Sec6 in exocytosis.
However, the relationship between Sec6 and PP2A in the Raf-MEK-ERK-p90RSK cascade is still largely unclear. We demonstrate that Sec6 regulates PP2A phosphatase activity through the modulation of the binding of PP2A-A and PP2Ac subunit, thereby modulating the phosphorylation of p90RSK at Thr359 and Ser380 and glycogen synthase kinase 3β at Ser9 and the expression of zinc finger E-box binding homeobox 1 (ZEB1), Vimentin, and zonula occludens 3 (ZO-3).

Free Research Field

組織学

Academic Significance and Societal Importance of the Research Achievements

今回の研究において、開口分泌小胞の構成要素の１つであるSec6が、細胞内でのある特定タンパク質の脱リン酸化に関与し、様々な疾患に関わる可能性を提示した。開口分泌小胞は、唾液、血液、尿に含まれており、現在では比較的容易に回収・解析が可能である。開口分泌小胞の構成要素の研究が進み、様々な病態に関与することがさらに解明されれば、非侵襲的な方法で病気の早期発見や病態把握に寄与できる。また、開口分泌小胞の構成要素をターゲットとした新たな薬剤の開発につながると考えられる。