Intercellular and intracellular cilia orientation is coordinated by CELSR1 and CAMSAP3 in oviduct multi-ciliated cells
Intercellular and intracellular cilia orientation is coordinated by CELSR1 and CAMSAP3 in oviduct multi-ciliated cells
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DOI：
10.1242/jcs.257006
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发表时间：
2021-01
影响因子：
4
通讯作者：
F. Usami;Masaki Arata;Dongbo Shi;Sanae Oka;Yoko Higuchi;F. Tissir;M. Takeichi;T. Fujimori
中科院分区：
文献类型：
--
作者：
F. Usami;Masaki Arata;Dongbo Shi;Sanae Oka;Yoko Higuchi;F. Tissir;M. Takeichi;T. Fujimori
摘要纤毛取向在多纤毛细胞(MCC)内部和之间协调的分子机制尚不完全清楚。在小鼠输卵管中，MCC沿组织轴呈特征性的基底体(BB)取向和微管梯度。在缺乏CELSR1(钙粘蛋白EGF滞后七通道G型受体1)的细胞中，细胞内的极性适度维持，尽管细胞间的极性协调被破坏。CELSR1是一种参与组织极性调节的平面细胞极性(PCP)因子。然而，微管负端调节因子CAMSAP3(钙调蛋白调节的光谱蛋白相关蛋白3)被发现是决定细胞内BB定位的关键。CAMSAP3以极化的方式定位在纤毛的底部，其突变导致细胞内BB取向的协调中断，以及连接BB的微管的组装，而不影响PCP因子的定位。因此，CELSR1和CAMSAP3都负责BB的定位，但以不同的方式；因此，它们的合作对于产生功能性的多纤毛组织至关重要。摘要：CELSR1和CAMSAP3负责细胞间和细胞内的基底体定位，它们的合作对于在小鼠输卵管中产生功能性的多纤毛上皮至关重要。
ABSTRACT 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. Summary: CELSR1 and CAMSAP3 are responsible for intercellular and intracellular basal body orientation, and their cooperation is critical for generating functional multi-ciliated epithelium in the mouse oviduct.