The role of epithelial barrier in Drosophila intestinal homeostasis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06650
• 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: National Institute for Physiological Sciences
• Principal Investigator: Yasushi Izumi 生理学研究所, 生体機能調節研究領域, 准教授 (10373268)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 上皮バリア / 組織恒常性 / 幹細胞 / ショウジョウバエ / 細胞増殖 / セプテートジャンクション / 細胞間接着 / 腸管

Outline of Final Research Achievements

In the Drosophila intestine, smooth septate junctions s(SJs) act as paracellular diffusion barrier. We identified four sSJ-associated membrane proteins, Ssk, Mesh, Tsp2A and Hoka, all of which are essential for sSJ organization and intestinal barrier function. We investigated the effect of sSJ protein depletion on the adult intestine. The sSJ protein-deficient flies showed intestinal hypertrophy, which was associated with increased intestinal stem cell proliferation and activation of the MAPK and Jak-Stat pathways in the stem cells. In the sSJ protein-deficient intestine, atypical protein kinase C (aPKC) was upregulated in the cytoplasm and the apical membrane of epithelial cells. The reduced expression of aPKC in the sSJ protein-deficient enterocytes resulted in reduced stem cell overproliferation. These findings indicate that sSJ proteins play a crucial role in maintaining stem cell homeostasis through the regulation of aPKC activities in the Drosophila intestine.

Free Research Field

細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

ショウジョウバエの腸管バリア機能に重要な役割を果たしているスムースセプテートジャンクション(sSJ)の新規構成分子Hokaを同定し、sSJの分子構築と形成機構の理解が進んだ。sSJ構成分子欠失により、腸管幹細胞の増殖が亢進し腸管に腫瘍が形成されたことから、上皮バリアが腸管幹細胞の増殖制御に重要な役割を果たしていることが明らかになった。
本研究より、ショウジョウバエ腸管の上皮バリアが、体内への異物の侵入あるいは体外への生体成分の流出を防ぐだけでなく、幹細胞の増殖のコントロールを介して腸管恒常性維持にも寄与することが明らかになった。