Prevo Bram, Scholey Jonathan M, Peterman Erwin J G
Department of Cellular & Molecular Medicine, University of California San Diego, CA, USA.
Ludwig Institute for Cancer Research, San Diego, CA, USA.
FEBS J. 2017 Sep;284(18):2905-2931. doi: 10.1111/febs.14068. Epub 2017 Apr 18.
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium. Following its discovery in Chlamydomonas, IFT has emerged as a powerful model system for studying general principles of motor-dependent cargo transport and we now appreciate the diversity that exists in the mechanism of IFT within cilia of different cell types. The absence of heterotrimeric kinesin-2 function, for example, causes a complete loss of both IFT and cilia in Chlamydomonas, but following its loss in Caenorhabditis elegans, where its primary function is loading the IFT machinery into cilia, homodimeric kinesin-2-driven IFT persists and assembles a full-length cilium. Generally, heterotrimeric kinesin-2 and IFT dynein motors are thought to play widespread roles as core IFT motors, whereas homodimeric kinesin-2 motors are accessory motors that mediate different functions in a broad range of cilia, in some cases contributing to axoneme assembly or the delivery of signaling molecules but in many other cases their ciliary functions, if any, remain unknown. In this review, we focus on mechanisms of motor action, motor cooperation, and motor-dependent cargo delivery during IFT.
鞭毛内运输（IFT）是一种依赖马达蛋白的货物运输形式，对于纤毛的组装、维持和长度控制至关重要，而纤毛在几乎所有真核细胞的运动、感觉接收和信号转导中都发挥着关键作用。在IFT过程中，正向驱动蛋白-2和逆向IFT动力蛋白驱动IFT列车的双向运输，将货物（例如微管蛋白等轴丝前体以及信号转导机制的分子）运送到纤毛内的组装位点。自其在衣藻中被发现以来，IFT已成为研究依赖马达蛋白的货物运输一般原理的强大模型系统，并且我们现在认识到不同细胞类型的纤毛内IFT机制存在多样性。例如，缺乏异源三聚体驱动蛋白-2的功能会导致衣藻中IFT和纤毛完全丧失，但在秀丽隐杆线虫中该功能丧失后，其主要功能是将IFT机制加载到纤毛中，由同型二聚体驱动蛋白-2驱动的IFT持续存在并组装出全长纤毛。一般来说，异源三聚体驱动蛋白-2和IFT动力蛋白被认为作为核心IFT马达蛋白发挥广泛作用，而同型二聚体驱动蛋白-2马达蛋白是辅助马达蛋白，在广泛的纤毛中介导不同功能，在某些情况下有助于轴丝组装或信号分子的运输，但在许多其他情况下，它们的纤毛功能（如果有的话）仍然未知。在这篇综述中，我们聚焦于IFT过程中马达蛋白作用、马达蛋白协作以及依赖马达蛋白的货物运输机制。
