Analysis for the ubiquitination of the planar cell polarity factors during neural tube closure.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Fujita Health University
• Principal Investigator: Nagaoka Tadahiro 藤田医科大学, 医科学研究センター, 助教 (70634864)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 平面内細胞極性 / ユビキチン / 神経管閉鎖

Outline of Final Research Achievements

The planar cell polarity (PCP) is the apical and vertical cell polarity. One of the mechanisms of polarity formation is degradation by ubiquitination of PCP factors, but the details remain unclear. We revealed that Vangl2 promotes the ubiquitination and degradation of Prickle2. However, the molecules responsible for the ubiquitination of Prickle2 have not been identified. Therefore, we aim to comprehensively analyze and identify this molecule by mass spectrometry. We have so far found novel molecules RBX1 and MAGEF1 that bind to this complex. The latter was found to suppress the degradation of the Prickle protein upon gene knockdown in cells. Although not a molecule involved in ubiquitination, it was revealed that N-cadherin, an adhesion molecule found to interact with Vangl2, is involved in neural tube closure through genetic interaction with Vangl2. Further analysis of this interaction was performed.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

Prickleをユビキチン化させる新規因子を解析することは、私たちの体の形を制御するのに重要な役割を果たしている平面内細胞極性形成のメカニズムの一端を明らかにすることができる。また、Nカドヘリン変異マウスやVangl2変異マウスを用いることで神経管閉鎖に於けるPrickleのユビキチン化を解析しその重要性を議論できる。また、それによって平面内細胞極性の形成過程の一端や、二分脊椎の病態の解明につながる結果が得られる可能性もあり、基礎医学から将来の臨床医学まで貢献できると考えられる。