Regulation of the actin dynamics by high-frequency tyrosine phosphorylation of MAP1B in the neuronal growth cone.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15897
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Niigata University
• Principal Investigator: Ito Yasuyuki 新潟大学, 医歯学系, 助教 (70710573)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳発生過程 / リン酸化プロテオミクス / 微小管結合タンパク質

Outline of Final Research Achievements

Protein tyrosine phosphorylation is known to be strongly activated in the developing neuron. I found that microtubule-associated protein 1B (MAP1B), was highly phosphorylated at Y1685 (pY1685-MAP1B) in the embryonic mouse brain. Although functions of pY1685-MAP1B were unclear, I found that overexpression of phosphomimetic MAP1B caused the abnormal morphology in growth cone, suggesting that pY1685-MAP1B interact with F-actin there. Furthermore, I revealed that the axon of phosphomimetic MAP1B-overexpressed neuron grew in the abnormal directions. Since phosphoproteomic results showed that pY1685-MAP1B was identified in the various regions of the developing brain, I concluded that this phosphorylation contributes to the construction of normal neuronal circuits.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

発生過程の脳はチロシンリン酸化が活発な場であることは古くから知られていたが、どの分子が良くリン酸化されているのかという定量的なアプローチは行われておらず、その意義は不明なままであった。本研究課題の遂行により、pY1685-MAP1Bが成長円錐の形態制御を介して、正常な脳発生過程の進行や正しい神経回路を構築するために貢献している分子である可能性が得られたことから、なぜ脳発生過程ではチロシンリン酸化活性が高い必要があるのか、その答えを出す一助になることが強く期待される。