Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Cell Rep. 2017 Sep 19;20(12):2792-2799. doi: 10.1016/j.celrep.2017.08.076.
Although microtubule motors mediate intracellular virus transport, the underlying interactions and control mechanisms remain poorly defined. This is particularly true for HIV-1 cores, which undergo complex, interconnected processes of cytosolic transport, reverse transcription, and uncoating of the capsid shell. Although kinesins have been implicated in regulating these events, curiously, there are no direct kinesin-core interactions. We recently showed that the capsid-associated kinesin-1 adaptor protein, fasciculation and elongation protein zeta-1 (FEZ1), regulates HIV-1 trafficking. Here, we show that FEZ1 and kinesin-1 heavy, but not light, chains regulate not only HIV-1 transport but also uncoating. This required FEZ1 phosphorylation, which controls its interaction with kinesin-1. HIV-1 did not stimulate widespread FEZ1 phosphorylation but, instead, bound microtubule (MT) affinity-regulating kinase 2 (MARK2) to stimulate FEZ1 phosphorylation on viral cores. Our findings reveal that HIV-1 binds a regulatory kinase to locally control kinesin-1 adaptor function on viral cores, thereby regulating both particle motility and uncoating.
尽管微管马达介导细胞内病毒运输,但潜在的相互作用和控制机制仍未得到明确界定。这对于 HIV-1 核心来说尤其如此,HIV-1 核心经历了复杂的、相互关联的细胞质运输、逆转录和衣壳壳的脱壳过程。尽管驱动蛋白已被牵连到这些事件的调节中,但奇怪的是,并没有直接的驱动蛋白-核心相互作用。我们最近表明,与衣壳相关的驱动蛋白-1 衔接蛋白,成束和延伸蛋白 zeta-1(FEZ1),调节 HIV-1 的运输。在这里,我们表明 FEZ1 和驱动蛋白-1 重链,但不是轻链,不仅调节 HIV-1 的运输,还调节脱壳。这需要 FEZ1 的磷酸化,这控制了它与驱动蛋白-1 的相互作用。HIV-1 并没有刺激广泛的 FEZ1 磷酸化,而是结合微管(MT)调节激酶 2(MARK2)来刺激病毒核心上的 FEZ1 磷酸化。我们的发现揭示了 HIV-1 结合调节激酶来局部控制病毒核心上的驱动蛋白-1 衔接蛋白功能,从而调节颗粒的运动和脱壳。