Identification of molecular machinery to control the selective/preferential binding of kinesin KIF5C to axonal microtubules by proximity labelling

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15112
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Li Xue (馬場雪) 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (50936507)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: KIF5C / Kinesin 1 / Microtubule binding / Cortical neuron

Outline of Final Research Achievements

In this study, we focus on the identification of molecular machinery in cells regulating or adjusting the binding affinity of KIF5C (Kinesin 1) to microtubules, of which the importance has been highlighted after the analysis of KIF5C mutants found in patients with severe malformations of cortical development and microcephaly. We made several KIF5C binding constructs to mimic selective binding and have established KIF5C-TurboID and KIF5C-APEX2 to label key protein players in semi-intact cortical neurons. We are now proceeding to hits identification using mass spectrometry analyses. We expect to reveal key regulators of KIF5C binding that could be potentially helpful for early diagnosis and treatment of the related brain diseases.

Free Research Field

Cytoskeleton, Cell biology

Academic Significance and Societal Importance of the Research Achievements

KIF5C変異体は、大脳皮質発達の重篤な奇形や小頭症の患者で発見され、その重要性が明らかになっている。本研究では、KIF5C（キネシン1）の微小管への結合親和性を制御する細胞内分子機構の同定を目指した。KIF5C結合の主要な制御因子が明らかになれば、関連する脳疾患の早期診断や治療に役立つ可能性がある。