Department of Biochemistry and Molecular Biology, USUHS, Bethesda, MD 20814, USA.
J Cell Sci. 2010 Oct 15;123(Pt 20):3596-604. doi: 10.1242/jcs.075259. Epub 2010 Sep 28.
Cytoplasmic dynein in filamentous fungi accumulates at microtubule plus-ends near the hyphal tip, which is important for minus-end-directed transport of early endosomes. It was hypothesized that dynein is switched on at the plus-end by cargo association. Here, we show in Aspergillus nidulans that kinesin-1-dependent plus-end localization is not a prerequisite for dynein ATPase activation. First, the Walker A and Walker B mutations in the dynein heavy chain AAA1 domain implicated in blocking different steps of the ATPase cycle cause different effects on dynein localization to microtubules, arguing against the suggestion that ATPase is inactive before arriving at the plus-end. Second, dynein from ΔkinA (kinesin 1) mutant cells has normal ATPase activity despite the absence of dynein plus-end accumulation. In ΔkinA hyphae, dynein localizes along microtubules and does not colocalize with abnormally accumulated early endosomes at the hyphal tip. This is in contrast to the colocalization of dynein and early endosomes in the absence of NUDF/LIS1. However, the Walker B mutation allows dynein to colocalize with the hyphal-tip-accumulated early endosomes in the ΔkinA background. We suggest that the normal ability of dyenin to interact with microtubules as an active minus-end-directed motor demands kinesin-1-mediated plus-end accumulation for effective interactions with early endosomes.
丝状真菌中的细胞质动力蛋白在菌丝尖端附近的微管正端积累,这对于早期内体的负端导向运输很重要。有人假设动力蛋白通过货物结合在正端被激活。在这里,我们在构巢曲霉中表明,驱动蛋白-1 依赖性的正端定位不是动力蛋白 ATP 酶激活的先决条件。首先,在 AAA1 结构域中的 Walker A 和 Walker B 突变,该结构域涉及阻止 ATP 酶循环的不同步骤,对动力蛋白定位到微管的影响不同,这与在到达正端之前 ATP 酶没有活性的说法相矛盾。其次,尽管没有动力蛋白的正端积累,来自 ΔkinA(驱动蛋白 1)突变细胞的动力蛋白仍具有正常的 ATP 酶活性。在 ΔkinA 菌丝中,动力蛋白沿微管定位,并且不在菌丝尖端与异常积累的早期内体共定位。这与在没有 NUDF/LIS1 的情况下动力蛋白和早期内体的共定位形成对比。然而,Walker B 突变允许动力蛋白与 ΔkinA 背景中的菌丝尖端积累的早期内体共定位。我们认为,动力蛋白作为一种活跃的负端导向马达与微管正常相互作用的能力需要驱动蛋白-1 介导的正端积累,以实现与早期内体的有效相互作用。