Analysis of multiple mechanisms of APP axonal transport

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15270
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Doshisha University (2023); Hokkaido University (2022)
• Principal Investigator: Sobu Yuriko 同志社大学, 脳科学研究科, 助教 (80825068)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 軸索輸送 / APP / アミロイド前駆体タンパク質 / 細胞内輸送 / キネシン1

Outline of Final Research Achievements

Several mechanism of axonal transport of amyloid precursor protein (APP) have reported. In this study, se showed that there is a different molecular mechanism for axonal transport of APP. We also found that this difference is due to multiple kinesin Isoforms. APP interacts with new identified kinesin by a mechanism quite different from known molecular mechanisms. In most cases, APP is transported toward axon terminals in a more rapid manner, but knockdown of the molecules responsible for this transport did not inhibit APP axonal transport. Simultaneous knockdown of the newly identified molecules in this study inhibited most APP transport, indicating that a novel transport mechanism is indeed functioning in neurons.

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Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、APPの軸索輸送機構について複数の分子メカニズムが提唱されてきたが、関連分子のノックダウンがAPP輸送を完全に停止させないなど、輸送機構の複雑さが提唱されてきた。本研究は1つの軸索の中で、APPが複数のメカニズムにより輸送されていることを明らかにしたものであり、今後の軸索輸送機構の議論をより正確にするための土台になりうる。APPはアルツハイマー関連分子としてだけではなく、発生期やシナプス形成の機能も報告されており、同定した輸送機構は軸索外の機能に関与する可能性も考えられる。