Planar cell polarity induces local microtubule bundling for coordinated ciliary beating

平面细胞极性诱导局部微管捆绑,实现纤毛协调摆动

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作者:Shogo Nakayama, Tomoki Yano, Toshinori Namba, Satoshi Konishi, Maki Takagishi, Elisa Herawati, Tomoki Nishida, Yasuo Imoto, Shuji Ishihara, Masahide Takahashi, Ken'ya Furuta, Kazuhiro Oiwa, Atsushi Tamura, Sachiko Tsukita

Abstract

Multiciliated cells (MCCs) in tracheas generate mucociliary clearance through coordinated ciliary beating. Apical microtubules (MTs) play a crucial role in this process by organizing the planar cell polarity (PCP)-dependent orientation of ciliary basal bodies (BBs), for which the underlying molecular basis remains elusive. Herein, we found that the deficiency of Daple, a dishevelled-associating protein, in tracheal MCCs impaired the planar polarized apical MTs without affecting the core PCP proteins, causing significant defects in the BB orientation at the cell level but not the tissue level. Using live-cell imaging and ultra-high voltage electron microscope tomography, we found that the apical MTs accumulated and were stabilized by side-by-side association with one side of the apical junctional complex, to which Daple was localized. In vitro binding and single-molecule imaging revealed that Daple directly bound to, bundled, and stabilized MTs through its dimerization. These features convey a PCP-related molecular basis for the polarization of apical MTs, which coordinate ciliary beating in tracheal MCCs.

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