Blisnick Thierry, Buisson Johanna, Absalon Sabrina, Marie Alexandra, Cayet Nadège, Bastin Philippe
Trypanosome Cell Biology Unit, Institut Pasteur, and Centre National de la Recherche Scientifique URA 2581, 75015 Paris, France.
Imagopole Platform, Institut Pasteur, 75015 Paris, France.
Mol Biol Cell. 2014 Sep 1;25(17):2620-33. doi: 10.1091/mbc.E14-05-0961. Epub 2014 Jul 2.
Cilia and flagella are assembled by intraflagellar transport (IFT) of protein complexes that bring tubulin and other precursors to the incorporation site at their distal tip. Anterograde transport is driven by kinesin, whereas retrograde transport is ensured by a specific dynein. In the protist Trypanosoma brucei, two distinct genes encode fairly different dynein heavy chains (DHCs; ∼40% identity) termed DHC2.1 and DHC2.2, which form a heterodimer and are both essential for retrograde IFT. The stability of each heavy chain relies on the presence of a dynein light intermediate chain (DLI1; also known as XBX-1/D1bLIC). The presence of both heavy chains and of DLI1 at the base of the flagellum depends on the intermediate dynein chain DIC5 (FAP133/WDR34). In the IFT140(RNAi) mutant, an IFT-A protein essential for retrograde transport, the IFT dynein components are found at high concentration at the flagellar base but fail to penetrate the flagellar compartment. We propose a model by which the IFT dynein particle is assembled in the cytoplasm, reaches the base of the flagellum, and associates with the IFT machinery in a manner dependent on the IFT-A complex.
纤毛和鞭毛由蛋白质复合物的鞭毛内运输(IFT)组装而成,这些蛋白质复合物将微管蛋白和其他前体物质带到其远端的掺入位点。顺行运输由驱动蛋白驱动,而逆行运输则由一种特定的动力蛋白确保。在原生生物布氏锥虫中,两个不同的基因编码了相当不同的动力蛋白重链(DHCs;约40%的同一性),称为DHC2.1和DHC2.2,它们形成异源二聚体,对逆行IFT都是必不可少的。每个重链的稳定性依赖于动力蛋白轻中间链(DLI1;也称为XBX-1/D1bLIC)的存在。鞭毛基部重链和DLI1的存在取决于中间动力蛋白链DIC5(FAP133/WDR34)。在IFT140(RNAi)突变体中,一种对逆行运输必不可少的IFT-A蛋白,IFT动力蛋白成分在鞭毛基部以高浓度存在,但无法穿透鞭毛区室。我们提出了一个模型,通过该模型,IFT动力蛋白颗粒在细胞质中组装,到达鞭毛基部,并以依赖于IFT-A复合物的方式与IFT机制结合。