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Publication : Excess centrosomes disrupt endothelial cell migration via centrosome scattering.

First Author  Kushner EJ Year  2014
Journal  J Cell Biol Volume  206
Issue  2 Pages  257-72
PubMed ID  25049273 Mgi Jnum  J:215833
Mgi Id  MGI:5607186 Doi  10.1083/jcb.201311013
Citation  Kushner EJ, et al. (2014) Excess centrosomes disrupt endothelial cell migration via centrosome scattering. J Cell Biol 206(2):257-72
abstractText  Supernumerary centrosomes contribute to spindle defects and aneuploidy at mitosis, but the effects of excess centrosomes during interphase are poorly understood. In this paper, we show that interphase endothelial cells with even one extra centrosome exhibit a cascade of defects, resulting in disrupted cell migration and abnormal blood vessel sprouting. Endothelial cells with supernumerary centrosomes had increased centrosome scattering and reduced microtubule (MT) nucleation capacity that correlated with decreased Golgi integrity and randomized vesicle trafficking, and ablation of excess centrosomes partially rescued these parameters. Mechanistically, tumor endothelial cells with supernumerary centrosomes had less centrosome-localized gamma-tubulin, and Plk1 blockade prevented MT growth, whereas overexpression rescued centrosome gamma-tubulin levels and centrosome dynamics. These data support a model whereby centrosome-MT interactions during interphase are important for centrosome clustering and cell polarity and further suggest that disruption of interphase cell behavior by supernumerary centrosomes contributes to pathology independent of mitotic effects.
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