Functions of glycosylation in integrin-mediated outside-in and inside-out signaling

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03184
• 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: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Gu Jianguo 東北医科薬科大学, 薬学部, 教授 (40260369)
• Co-Investigator(Kenkyū-buntansha): 福田 友彦 東北医科薬科大学, 薬学部, 准教授 (40433510) ; 伊左治 知弥 東北医科薬科大学, 薬学部, 准教授 (80433514)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 糖鎖 / 細胞接着

Outline of Final Research Achievements

Integrins are heterodimers composed of α and β subunits, serving as major receptors for the extracellular matrix. It has been revealed that they control the sialylation of N-glycans by binding focal adhesion kinase (FAK) to the intracellular domain of integrin β1. On the other hand, we have elucidated the role of intracellular O-GlcNAc modification in cell adhesion and its control over the biosynthesis of branched N-glycans expressed on the cell surface. We have also discovered the occurrence of O-GlcNAc modification on FAK. This study provides the first evidence of the involvement of glycans in the regulation of outside-in and inside-out signaling mediated by integrins, highlighting the relevance and significance of glycan expression both intracellularly and extracellularly.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

インテグリンは、細胞の増殖・生存などの生理的な過程のみならず、がん細胞の増殖・転移・浸潤など病理的な過程にも重要な役割を担っている。本研究は、国内・国外において全く行われていない、インテグリンが媒介するシグナルにおける糖鎖による制御、また細胞接着・移動・増殖における細胞内のO-GlcNAcと細胞表面の糖鎖との関連性及びその意義を明らかにすることで、「糖鎖による細胞接着・移動・増殖の動態制御」という新たな分子機構の導入を目指す。