The mechanism of LOT formation by LOTUS as an endogenous Nogo receptor-1 antagonist

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830015
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Yokohama City University
• Principal Investigator: IKETANI Masumi 横浜市立大学, 生命医科学研究科, 共同研究員 (60644359)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 軸索側枝 / 神経回路形成 / Nogo / NgR1 / LOTUS

Outline of Final Research Achievements

Previously, we identified LOT usher substance (LOTUS) as an endogenous Nogo receptor-1 (NgR1) antagonist and found that LOTUS contributes to formation of LOT axonal bundle through its antagonistic action towards NgR1 function. The NgR1 is a receptor of axonal outgrowth inhibitors such as Nogo. We examined in vivo phenotypes in the axonal branching in LOT of LOTUS-KO and/or NgR1-KO mice. The collateral branches of LOT were increased in LOTUS-KO mice, whereas the collateral branches were decreased in NgR1-KO mice. Moreover, the abnormal increase of axonal branching seen in LOTUS-KO mice was rescued in double mutant of LOTUS- and NgR1-KO mice. These findings suggest that Nogo-A and NgR1 interaction may contribute to axonal branching in LOT development. Thus, it is considered that LOT formation is developmentally controlled by Nogo-A induction and down-regulation of the antagonistic action towards Nogo-NgR1 signaling by LOTUS.

Free Research Field

神経生物学