Department of Biomedicine, University of Bergen, Norway; Institute of Cell Biology and Immunology, University of Stuttgart, Germany.
Department of Biomedicine, University of Bergen, Norway.
Exp Cell Res. 2020 May 15;390(2):111961. doi: 10.1016/j.yexcr.2020.111961. Epub 2020 Mar 21.
N-alpha-acetyltransferase 80 (NAA80) was recently demonstrated to acetylate the N-terminus of actin, with NAA80 knockout cells showing actin cytoskeleton-related phenotypes, such as increased formation of membrane protrusions and accelerated migration. Here we report that NAA80 knockout cells additionally display fragmentation of the Golgi apparatus. We further employed rescue assays to demonstrate that this phenotype is connected to the ability of NAA80 to modify actin. Thus, re-expression of NAA80, which leads to re-establishment of actin's N-terminal acetyl group, rescued the Golgi fragmentation, whereas a catalytic dead NAA80 mutant could neither restore actin Nt-acetylation nor Golgi structure. The Golgi phenotype of NAA80 KO cells was shared by both migrating and non-migrating cells and live-cell imaging indicated increased Golgi dynamics in migrating NAA80 KO cells. Finally, we detected a drastic increase in the amount of F-actin in cells lacking NAA80, suggesting a causal relationship between this effect and the observed re-organization of Golgi structure. The findings further underscore the importance of actin Nt-acetylation and provide novel insight into its cellular roles, suggesting a mechanistic link between actin modification state and Golgi organization.
N-α-乙酰基转移酶 80（NAA80）最近被证明可以乙酰化肌动蛋白的 N 端，NAA80 敲除细胞表现出与肌动蛋白细胞骨架相关的表型，例如膜突形成增加和迁移加速。在这里，我们报告说 NAA80 敲除细胞还显示出高尔基体的碎片化。我们进一步采用挽救实验证明，这种表型与 NAA80 修饰肌动蛋白的能力有关。因此，重新表达 NAA80，导致肌动蛋白 N 端乙酰化的重新建立，挽救了高尔基体的碎片化，而缺乏催化活性的 NAA80 突变体既不能恢复肌动蛋白 Nt-乙酰化，也不能恢复高尔基体结构。NAA80 KO 细胞的高尔基体表型在迁移和非迁移细胞中均存在，活细胞成像表明迁移的 NAA80 KO 细胞中高尔基体动力学增加。最后，我们检测到缺乏 NAA80 的细胞中 F-肌动蛋白的数量急剧增加，这表明这种效应与观察到的高尔基体结构重新组织之间存在因果关系。这些发现进一步强调了肌动蛋白 N 端乙酰化的重要性，并为其细胞作用提供了新的见解，表明肌动蛋白修饰状态和高尔基体组织之间存在机制联系。
