Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Cell Host Microbe. 2013 Nov 13;14(5):535-46. doi: 10.1016/j.chom.2013.10.012.
Stable microtubule (MT) subsets form distinct networks from dynamic MTs and acquire distinguishing posttranslational modifications, notably detyrosination and acetylation. Acting as specialized tracks for vesicle and macromolecular transport, their formation is regulated by the end-binding protein EB1, which recruits proteins that stabilize MTs. We show that HIV-1 induces the formation of acetylated and detyrosinated stable MTs early in infection. Although the MT depolymerizing agent nocodazole affected dynamic MTs, HIV-1 particles localized to nocodazole-resistant stable MTs, and infection was minimally affected. EB1 depletion or expression of an EB1 carboxy-terminal fragment that acts as a dominant-negative inhibitor of MT stabilization prevented HIV-1-induced stable MT formation and suppressed early viral infection. Furthermore, we show that the HIV-1 matrix protein targets the EB1-binding protein Kif4 to induce MT stabilization. Our findings illustrate how specialized MT-binding proteins mediate MT stabilization by HIV-1 and the importance of stable MT subsets in viral infection.
稳定微管 (MT) 亚群与动态 MT 形成独特的网络，并获得不同的翻译后修饰，特别是去酪氨酸化和乙酰化。作为囊泡和大分子运输的专用轨道，它们的形成受末端结合蛋白 EB1 调节，EB1 招募稳定 MT 的蛋白质。我们发现 HIV-1 在感染早期诱导乙酰化和去酪氨酸化的稳定 MT 的形成。虽然微管解聚剂诺考达唑影响动态 MT，但 HIV-1 颗粒定位于诺考达唑抗性稳定 MT，感染受到最小影响。EB1 耗竭或表达作为 MT 稳定的显性负抑制剂的 EB1 羧基末端片段可防止 HIV-1 诱导的稳定 MT 形成并抑制早期病毒感染。此外，我们表明 HIV-1 基质蛋白将 EB1 结合蛋白 Kif4 靶向以诱导 MT 稳定。我们的研究结果说明了 HIV-1 如何通过专门的 MT 结合蛋白介导 MT 稳定，以及稳定 MT 亚群在病毒感染中的重要性。
