Planar polarity of microtubules

2023 Fiscal Year Final Research Report

• Project/Area Number: 17K15593
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Nagoya City University (2023); Nagoya University (2017-2019)
• Principal Investigator: Takagishi Maki 名古屋市立大学, 医薬学総合研究院(薬学), 助教 (10723918)
• Project Period (FY): 2023-05-26 – 2024-03-31
• Keywords: 微小管 / 平面内細胞極性 / 繊毛

Outline of Final Research Achievements

Cilia are docked on apical cell surfaces, and their orientation is determined by planar polarity at the apical cell cortex. Coordinated beatings of multiple motile cilia with coordinated orientation generate directional fluid flow on the tissue surface.
Microtubules, a principal component of the cytoskeleton, asymmetrically localize to the apical cell membrane of multi-ciliated ependymal cells lining the lateral ventricular wall on the side that contacts cerebrospinal fluid flow. Individual ependymal cells have planar polarized microtubules that connect ciliary base to coordinate cilia orientation.
We found that cytoplasmic dynein is anchored to the one side of cell cortex that regulates microtubule dynamics. This is required for coordinated cilia orientation on the LV wall.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、脳室内の繊毛の向きが揃うメカニズムを解明しました。脳室内の繊毛の向きが揃うことで、脳脊髄液が脳室出口に向かって流れることができます。繊毛の向きを決定する因子に異常があると、繊毛が同じ方向へ波打つことができず、脳脊髄液の流れが乱れてしまいます。出口方向へ流出できなかった脳脊髄液は脳室内に停滞し、脳室が拡張して水頭症となります。水頭症は脳実質を圧迫して発達障害や認知症をもたらします。本研究で発見した細胞内分子機構によって、水頭症の発症機序や原因遺伝子の解明につながると期待されます。