Analysis of the molecular mechanism underlying a promoting effect of LOTUS on neurite outgrowth

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Shimane University (2023); Nagoya City University (2021-2022)
• Principal Investigator: KURIHARA Yuji 島根大学, 学術研究院医学・看護学系, 助教 (00634552)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経科学 / 薬理学 / 突起伸長 / 神経再生

Outline of Final Research Achievements

In this study, I analyzed the molecular mechanism by which LOTUS promotes neurite outgrowth. I found that LOTUS has a promoting effect on neurite outgrowth and the promoting effect is mediated by unidentified LOTUS-binding protein(s). By screening new LOTUS-binding protein(s), I identified some transmembrane proteins which are associated with neurite outgrowth. In gene knockdown experiment of these proteins, I found that the promoting effect of LOTUS on neurites is suppressed in the cells reducing the expression of a certain cell adhesion molecule. Furthermore, inhibition of an interaction between LOTUS and the cell adhesion molecule attenuated the promoting effect of LOTUS on neurite outgrowth. These data suggest LOTUS promotes neurite outgrowth through its interaction with the cell adhesion molecule.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、LOTUSが結合する新たな分子として細胞間接着因子を同定し、この細胞間接着因子との結合によってLOTUSは神経突起を伸長させることが明らかとなった。この成果は、神経突起伸長に関わる分子メカニズムを新たに解明しただけでなく、既に報告されているLOTUSの神経再生促進効果に関する新規の分子メカニズムを提唱するものだと考えられる。このことは神経再生を必要とする社会的ニーズに応える重要な知見となり得る。