p97ATPase/p47-mediated membrane tethering system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Kyushu University
• Principal Investigator: Kondo Hisao 九州大学, 医学研究院, 教授 (20205561)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膜融合 / ゴルジ体 / 小胞体 / p97ATPase

Outline of Final Research Achievements

VCIP135 is necessary for p97/p47-mediated Golgi membrane fusion. Although VCIP135 is known to form a complex with p97 in the cytosol, the role of this complex in Golgi and ER biogenesis has remained unclear. In this study, we demonstrated that VCIP135 has two distinct p97-binding sites at its N- and C-terminal regions. We also clarified that the N- and C-terminal binding sites in VCIP135 interact with the C- and N-terminal regions of p97, respectively. These two interactions within the complex are synchronously controlled by the nucleotide state of p97. We next generated VCIP135 mutants lacking each of the p97-binding sites to investigate their functions in living cells, and clarified that VCIP135 is involved in Golgi and ER biogenesis through its two distinct interactions with p97. VCIP135 is hence a unique p97-binding protein that functions by interacting with both the N-and C-terminal regions of p97, which strongly suggests that it plays crucial roles in p97-mediated events.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、VCIP135がp97ATPaseのN末端とC末端の両方にATP依存性に結合することを見いだしたが、このようなp97結合蛋白質は今まで知られていない。このことから我々はVCIP135がp97複合体の解離因子として働くという仮説を提唱した。特に新規係留装置であるFTCD-p97/p47-FTCD複合体においてp97はN末端とC末端でそれぞれFTCDとp47とに結合するが、VCIP135はその両方の結合を同時に解離し得る。またp97-p47間の結合が解離すると、p47-FTCD間の結合も弱くなり解離に至る。即ち、VCIP135が膜係留装置のリサイクル因子である可能性がある。