The mechanism of the tight junction morphology formation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02523
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: Furuse Mikio 生理学研究所, 生体機能調節研究領域, 教授 (90281089)
• Co-Investigator(Kenkyū-buntansha): 菅原 太一 熊本大学, 大学院先導機構, 助教 (30758412)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 上皮細胞 / タイトジャンクション / クローディン / 上皮バリア機能 / 細胞間接着

Outline of Final Research Achievements

The mechanism of tight junction (TJ) formation was analyzed by re-expressing claudin in TJ-deficient epithelial cells, which were established by deleting five claudin genes from the epithelial cell line MDCK cells. The results revealed that many claudin subtypes can form TJs by themselves, while some cannot; that the charge-selective channels formed by the pore-forming claudin subtypes are formed by the subtype alone and do not require the involvement of other subtypes; and that ZO-1, a scaffold protein interacting with claudins, is not required for positioning of TJ formation. Furthermore, we found that the TJ membrane proteins claudin and JAM-A cooperatively contribute to the homeostasis of the epithelial cell-cell adhesion complex.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

タイトジャンクションが形成する細胞間隙の水溶性分子に対する透過バリアは、腸管バリア、皮膚バリア、血液脳関門といった私達の生存に必須な生体内バリアを形作っている。したがって、タイトジャンクションの形成機構について新しい知見を得た本研究は、きわめて基礎的であるが、基礎医学的に重要であるばかりでなく、タイトジャンクション形成の人為的コントロールにより医学応用を目指す研究にも重要な示唆を与える。