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Centrosome amplification fine-tunes tubulin acetylation to differentially control intracellular organization

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 loss of dynein. Cells with amplified centrosomes display increased levels of acetylated tubulin, a PTM that could enhance kinesin-1 mediated transport. Depletion of -tubulin acetyltransferase 1 (TAT1) 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 indicates that the polarized distribution of modified microtubules, rather than levels alone, plays an important role in 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.

SUBMITTER: Dr. Pedro Monteiro

PROVIDER: S-SCDT-10_15252-EMBJ_2022112812 | biostudies-other |

REPOSITORIES: biostudies-other

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