BMP4调节小鼠结节性不动纤毛中Pkd2的非对称分布,以及左右决定所需的纤毛机械传感。

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY
Takanobu A Katoh, Tim Lange, Yoshiro Nakajima, Kenta Yashiro, Yasushi Okada, Hiroshi Hamada
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引用次数: 0

摘要

背景:小鼠结节状不动纤毛能机械地感知左右(L-R)决定的弯曲方向,并激活左侧特异性信号级联,导致结节活性增加。最近有报道称,L-R决定的关键通道Pkd2在不动纤毛上分布不对称。然而,不对称的 Pkd2 分布与依赖方向的流动感应之间的因果关系还不十分清楚。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)影响了Pkd2的分布。此外,使用光学镊子对结节性不动纤毛进行三维操作后发现,过量的 BMP4 会导致纤毛的机械感应能力出现缺陷:实验数据和模型计算结果表明,BMP4能调节Pkd2在结节状不动纤毛中的不对称分布,从而影响这些纤毛感知弯曲方向以确定L-R的能力。这项研究首次揭示了蛋白质在纤毛中的不对称分布与其功能之间的关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
BMP4 regulates asymmetric Pkd2 distribution in mouse nodal immotile cilia and ciliary mechanosensing required for left-right determination.

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.

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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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