Mechanisms of large cargo secretion and regulated secretion from external stimuli

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03203
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Akita University
• Principal Investigator: Saito Kota 秋田大学, 医学系研究科, 教授 (60549632)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 分泌 / 小胞体 / ER exit site / TANGO1 / Sec16

Outline of Final Research Achievements

Secretory proteins synthesized in the endoplasmic reticulum (ER) bud off from the ER exit sites (ERES) and are transported to the Golgi apparatus before being secreted outside the cells. ERES is the starting point of secretion, but its composition and regulatory mechanisms are not well understood. We discovered that TANGO1, isolated as a cargo receptor for collagen, cooperates with Sec16 to facilitate the formation of ERES. Additionally, we found that phosphorylation of TANGO1 by CK1 during mitosis leads to the disassembly of ERES during cell division. Furthermore, we revealed that Sec16 also undergoes CK1-mediated phosphorylation, which regulates its binding activity to ERES through liquid-liquid phase separation.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞からの分泌機構が明らかになれば、分泌が異常になったことによる疾患に対する治療法の開発等に貢献することができる。特に、TANGO1やSec16は分泌の出発点を制御する因子であり、その機能が明らかになれば、広範な分泌現象に対する制御方法の開発にもつながると期待できる。