Excess centrosomes perturb dynamic endothelial cell repolarization during blood vessel formation.

Autor:	Kushner EJ; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Ferro LS; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Yu Z; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Bautch VL; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 bautch@med.unc.edu.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2016 Jun 15; Vol. 27 (12), pp. 1911-20. Date of Electronic Publication: 2016 Apr 20.
DOI:	10.1091/mbc.E15-09-0645
Abstrakt:	Blood vessel formation requires dynamic movements of endothelial cells (ECs) within sprouts. The cytoskeleton regulates migratory polarity, and centrosomes organize the microtubule cytoskeleton. However, it is not well understood how excess centrosomes, commonly found in tumor stromal cells, affect microtubule dynamics and interphase cell polarity. Here we find that ECs dynamically repolarize during sprouting angiogenesis, and excess centrosomes block repolarization and reduce migration and sprouting. ECs with excess centrosomes initially had more centrosome-derived microtubules but, paradoxically, fewer steady-state microtubules. ECs with excess centrosomes had elevated Rac1 activity, and repolarization was rescued by blockade of Rac1 or actomyosin blockers, consistent with Rac1 activity promoting cortical retrograde actin flow and actomyosin contractility, which precludes cortical microtubule engagement necessary for dynamic repolarization. Thus normal centrosome numbers are required for dynamic repolarization and migration of sprouting ECs that contribute to blood vessel formation. (© 2016 Kushner et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
Databáze:	MEDLINE
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