Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji-cho, Okazaki, 444-8787 Japan.
Department of Basic Biology, School of Life Science, SOKENDAI, The Graduate University for Advanced Studies, 5-1 Higashiyama, Myodaiji-cho, Okazaki, 444-8787 Japan.
J Cell Sci. 2021 Feb 22;134(4):jcs257006. doi: 10.1242/jcs.257006.
The molecular mechanisms by which cilia orientation is coordinated within and between multi-ciliated cells (MCCs) are not fully understood. In the mouse oviduct, MCCs exhibit a characteristic basal body (BB) orientation and microtubule gradient along the tissue axis. The intracellular polarities were moderately maintained in cells lacking CELSR1 (cadherin EGF LAG seven-pass G-type receptor 1), a planar cell polarity (PCP) factor involved in tissue polarity regulation, although the intercellular coordination of the polarities was disrupted. However, CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a microtubule minus-end regulator, was found to be critical for determining the intracellular BB orientation. CAMSAP3 localized to the base of cilia in a polarized manner, and its mutation led to the disruption of intracellular coordination of BB orientation, as well as the assembly of microtubules interconnecting BBs, without affecting PCP factor localization. Thus, both CELSR1 and CAMSAP3 are responsible for BB orientation but in distinct ways; their cooperation should therefore be critical for generating functional multi-ciliated tissues.
目前尚未完全了解纤毛在多纤毛细胞（MCC）内和细胞之间定向协调的分子机制。在小鼠输卵管中，MCC 表现出特征性的基体（BB）定向和组织轴上的微管梯度。尽管细胞间极性的协调被破坏，但在缺乏参与组织极性调节的平面细胞极性（PCP）因子 CELSR1（钙粘蛋白 EGF LAG 七跨膜 G 型受体 1）的细胞中，细胞内极性仍得到适度维持。然而，微管负端调节剂 CAMSAP3 对于确定细胞内 BB 定向至关重要。CAMSAP3 以极化的方式定位于纤毛的基部，其突变导致 BB 定向的细胞内协调以及连接 BB 的微管的组装被破坏，而不影响 PCP 因子的定位。因此，CELSR1 和 CAMSAP3 都负责 BB 定向，但方式不同；因此，它们的合作对于产生功能性多纤毛组织至关重要。
