Abstract：
BACKGROUND: Mouse nodal immotile cilia mechanically sense the bending direction for left-right (L-R) determination and activate the left-side-specific signaling cascade, leading to increased Nodal activity. Asymmetric distribution of Pkd2, a crucial channel for L-R determination, on immotile cilia has been reported recently. However, the causal relationship between the asymmetric Pkd2 distribution and direction-dependent flow sensing is not well understood. Furthermore, the underlying molecular mechanism directing this asymmetric Pkd2 distribution remains unclear.
RESULTS: The effects of several recombinant proteins and inhibitors on the Pkd2 distribution were analyzed using super-resolution microscopy. Notably, bone morphogenetic protein 4 (BMP4) affected the Pkd2 distribution. Additionally, three-dimensional manipulation of nodal immotile cilia using optical tweezers revealed that excess BMP4 caused defects in the mechanosensing ability of the cilia.
CONCLUSIONS: Experimental data together with model calculations suggest that BMP4 regulates the asymmetric distribution of Pkd2 in nodal immotile cilia, thereby affecting the ability of these cilia to sense the bending direction for L-R determination. This study, for the first time, provides insight into the relationship between the asymmetric protein distribution in cilia and their function.
RESULTS: The effects of several recombinant proteins and inhibitors on the Pkd2 distribution were analyzed using super-resolution microscopy. Notably, bone morphogenetic protein 4 (BMP4) affected the Pkd2 distribution. Additionally, three-dimensional manipulation of nodal immotile cilia using optical tweezers revealed that excess BMP4 caused defects in the mechanosensing ability of the cilia.
CONCLUSIONS: Experimental data together with model calculations suggest that BMP4 regulates the asymmetric distribution of Pkd2 in nodal immotile cilia, thereby affecting the ability of these cilia to sense the bending direction for L-R determination. This study, for the first time, provides insight into the relationship between the asymmetric protein distribution in cilia and their function.
摘要：
背景：小鼠结节不运动纤毛机械感应弯曲方向以进行左右（L-R）确定，并激活左侧特异性信号级联，导致节点活性增加。Pkd2的非对称分布，L-R确定的关键通道，最近有关于不活动纤毛的报道。然而,不对称Pkd2分布与方向相关的流量传感之间的因果关系尚不清楚。此外，指导这种不对称Pkd2分布的潜在分子机制仍不清楚。
结果：使用超分辨率显微镜分析了几种重组蛋白和抑制剂对Pkd2分布的影响。值得注意的是,骨形态发生蛋白4（BMP4）影响Pkd2的分布。此外,使用光学镊子对结节不运动纤毛进行三维操作表明，过量的BMP4会导致纤毛的机械感应能力缺陷。
结论：实验数据和模型计算表明，BMP4调节Pkd2在结节不运动纤毛中的不对称分布，从而影响这些纤毛感知L-R测定的弯曲方向的能力。这项研究,第一次,提供了有关纤毛中不对称蛋白质分布及其功能之间关系的见解。
结果：使用超分辨率显微镜分析了几种重组蛋白和抑制剂对Pkd2分布的影响。值得注意的是,骨形态发生蛋白4（BMP4）影响Pkd2的分布。此外,使用光学镊子对结节不运动纤毛进行三维操作表明，过量的BMP4会导致纤毛的机械感应能力缺陷。
结论：实验数据和模型计算表明，BMP4调节Pkd2在结节不运动纤毛中的不对称分布，从而影响这些纤毛感知L-R测定的弯曲方向的能力。这项研究,第一次,提供了有关纤毛中不对称蛋白质分布及其功能之间关系的见解。
