鞭毛内运输列车可以切换轨道,并在完整的初级纤毛中沿着多条微管移动。

Intraflagellar transport trains can switch rails and move along multiple microtubules in intact primary cilia.

作者信息

Sun Shufeng, Liang Biqing, Koplas Adam, Tikhonenko Irina, Nachury Maxence, Khodjakov Alexey, Sui Haixin

机构信息

Wadsworth Center, New York State Department of Health, Albany, NY 12237.

Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY 12237.

出版信息

Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2413968122. doi: 10.1073/pnas.2413968122. Epub 2025 Apr 18.

Abstract

Structural homeostasis and proper distributions of signaling molecules in cilia require a constant flow of cargoes carried by intraflagellar transport (IFT) trains in both anterograde and retrograde directions within the thin, long ciliary shafts. In the motile cilium framework, the nine microtubule doublets of the same length serve as the transportation rails, and a preferential association to the two subtubules of the microtubule doublets prevents collisions among the IFT trains that move in opposite directions. However, this mechanism is incompatible with the primary cilia structure, where most of the nine microtubule doublets terminate in the ciliary shafts-only several of them reach the ciliary tip and only in a singlet form. Here, we demonstrate that anterograde and retrograde trains in primary cilia interact with both subtubules of the microtubule doublets without apparent preference. They can switch microtubules, and they may simultaneously interact with multiple microtubules to facilitate their movement. This architecture makes the collisions inevitable, and live-cell recordings reveal that anterograde and retrograde trains tend to pause when they come into direct contact. We also find that the velocity of the train's movement often changes after the pause. Thus, the motion behaviors of IFT trains in primary cilia are distinctive from those of motile cilia, and our data offer an essential foundation for understanding proper signaling molecule distributions in primary cilia.

摘要

纤毛中信号分子的结构稳态和适当分布需要由纤毛内运输(IFT)列车携带的货物在细长的纤毛轴内沿顺行和逆行方向持续流动。在运动性纤毛框架中,长度相同的九个微管双联体充当运输轨道,并且与微管双联体的两个亚管的优先结合可防止沿相反方向移动的IFT列车之间发生碰撞。然而,这种机制与初级纤毛结构不兼容,在初级纤毛结构中,九个微管双联体中的大多数在纤毛轴中终止,只有其中几个到达纤毛尖端并且仅以单重态形式存在。在这里,我们证明初级纤毛中的顺行和逆行列车与微管双联体的两个亚管相互作用,没有明显的偏好。它们可以切换微管,并且它们可能同时与多个微管相互作用以促进其移动。这种结构使得碰撞不可避免,活细胞记录显示顺行和逆行列车在直接接触时往往会暂停。我们还发现,列车运动的速度在暂停后经常会发生变化。因此,初级纤毛中IFT列车的运动行为与运动性纤毛的运动行为不同,我们的数据为理解初级纤毛中适当的信号分子分布提供了重要基础。

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