Integrated understanding of fundamental processes underlying formation of the endoplasmic reticulum network

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15218
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: SAKISAKA Toshiaki 神戸大学, 医学研究科, 教授 (80359843)
• Co-Investigator(Kenkyū-buntansha): 山本 泰憲 神戸大学, 医学研究科, 准教授 (30467659)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞小器官 / 小胞体 / 膜変形タンパク質

Outline of Final Research Achievements

Endoplasmic reticulum (ER) is a membrane-bound compartment composed of tubules and sheets in the cytoplasm. The ER tubules connect each other by three-way junctions, resulting in formation of the reticular ER network. While stability of the three-way junctions underlies dynamics of the reticular ER network, the molecular mechanism of how stability of the three-way junctions is regulated remains unclear.
In this study, we revealed that p120, a protein that bound to lunapark, negatively regulated the auto-ubiquitination and proteasomal degradation of lunapark, leading to stabilization of the three-way junctions. Moreover, we identified p57 as a novel ER membrane protein that localized to and regulated the three-way junctions.

Free Research Field

医化学一般

Academic Significance and Societal Importance of the Research Achievements

本研究のp120によるlunaparkの自己ユビキチン化を介した分解制御は、小胞体ネットワークの流動性に膜変形タンパク質の分解が大きな寄与をしていることを提示したものであり、学術的な意義が大きいと考えている。また、新規three-way junction局在分子p57の発見は、three-way junctionの動態制御の全容を理解する上で重要な知見である。小胞体ネットワークの破綻は遺伝性痙性対麻痺などの神経変性疾患を引き起こすことから、本研究の成果が神経変性疾患の発症機序の理解や治療薬の開発に繋がる可能性が考えられ、社会的にも意義が大きいと考えている。