中心体
生物
驱动蛋白
微管
细胞生物学
动力蛋白
微管蛋白
乙酰化
细胞器
内体
运动蛋白
细胞内
细胞
遗传学
细胞周期
基因
作者
Pedro T. Monteiro,Bongwhan Yeon,Samuel S. Wallis,Susana A. Godinho
标识
DOI:10.15252/embj.2022112812
摘要
Abstract Intracellular organelle organization is conserved in eukaryotic cells and is primarily achieved through active transport by motor proteins along the microtubule cytoskeleton. Microtubule post‐translational modifications (PTMs) can contribute to microtubule diversity and differentially regulate motor‐mediated transport. Here, we show that centrosome amplification, commonly observed in cancer and shown to promote aneuploidy and invasion, induces a global change in organelle positioning towards the cell periphery and facilitates nuclear migration through confined spaces. This reorganization requires kinesin‐1 and is analogous to the loss of dynein. Cells with amplified centrosomes display increased levels of acetylated tubulin, a PTM that could enhance kinesin‐1‐mediated transport. Depletion of α‐tubulin acetyltransferase 1 (αTAT1) to block tubulin acetylation rescues the displacement of centrosomes, mitochondria, and vimentin but not Golgi or endosomes. Analyses of the distribution of total and acetylated microtubules indicate that the polarized distribution of modified microtubules, rather than levels alone, plays an important role in the positioning of specific organelles, such as the centrosome. We propose that increased tubulin acetylation differentially impacts kinesin‐1‐mediated organelle displacement to regulate intracellular organization.
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