Functional analysis of a novel NELL-Robo signaling system in osteogenesis

2024 Fiscal Year Final Research Report

• Project/Area Number: 20H02948
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Nagoya University
• Principal Investigator: Niimi Tomoaki 名古屋大学, 生命農学研究科, 講師 (30377791)
• Co-Investigator(Kenkyū-buntansha): 水谷 公彦 京都大学, 農学研究科, 助教 (40314281)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 軸索誘導因子 / シグナル伝達

Outline of Final Research Achievements

The NELL1 gene was originally identified in craniosynostosis patients as being specifically upregulated within prematurely fusing sutures. Because of its potent osteoinductive activity, NELL1 protein may be useful for bone regeneration therapy. However, there is little knowledge regarding NELL1-mediated signaling pathways. In this study, we focused on the property that NELL1 and its novel receptor, ROBO2, bind only in acidic conditions to elucidate the signaling mechanism of the NELL－ROBO complex. The results revealed that the NELL1/2 and ROBO1/2/3 families bind in a pH-dependent manner, suggesting the existence of a pH-dependent signal transduction regulatory mechanism.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

骨再生療法への応用を目指して、骨形成能を有するNELL1タンパク質のシグナル伝達機構の解明に取り組み、NELLファミリーリガンドとその新奇受容体であるRoboファミリーのpH依存的な複合体形成のメカニズムを発見した。このことは細胞外pHの変動によるシグナル伝達制御機構が存在することを示唆しており、NELLおよびRoboファミリータンパク質がともに発現している組織や器官においては、細胞外pHの制御が疾患の治療や創薬のターゲットとなり得ることを示している。