Elucidation of the functional mechanisms of galectin lattices in pancreatic beta cells and understanding their pathophysiological significance

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Ohtsubo Kazuaki 熊本大学, 大学院生命科学研究部(保), 教授 (30525457)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖鎖 / ガレクチンラティス / 膵臓β細胞 / GLUT2 / エンドサイトーシス / Protein kinase C / Teneurin-3

Outline of Final Research Achievements

It is well known that the localization and function of transporters and channel molecules expressed on the plasma membrane are regulated by the formation of galectin lattices on the cell surface, which are formed by the binding of glycan chains of these molecules to galectins that exist extracellular space. However, the detailed mechanism has not been well elucidated. In this study, we analyzed the galectin-lattice complexes formed on the cell surface by mass spectrometry to elucidate the mechanism of the formation of the galectin-lattice and the endocytosis induced by the destruction of the galectin-lattice, and then analyzed their functions on the cellular physiological regulations. As a result, we succeeded in identifying anchor molecules required for galectin lattice formation at the plasma membrane and kinases involved in the endocytosis induced by the disassembly of the galectin-lattice.

Free Research Field

疾患糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

申請者らはこれまでの研究から膵臓β細胞におけるガレクチンラティスの崩壊が、グルコースセンサー分子であるGLUT2のエンドサイトーシスを惹起し、結果、血統レベルに応じたインスリン分泌機能が障害され、糖尿病を発症することを見出してきた。本提案研究により、その詳細な分子メカニズムの解明のための大きな手がかりを得ることに成功した。この成果は、細胞膜タンパク質のホメオスタシス機構の理解という学術的な意義があるのみならず、糖尿病などの代謝疾患の治療や、入院患者等の栄養管理で問題となるRefeeding syndromeの予防や患者のQOLの改善に繋がり、その社会的波意義や、臨床的意義は非常に大きい。