期刊
JOURNAL OF CELL BIOLOGY
卷 206, 期 1, 页码 97-112出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201401063
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- National Heart, Lung and Blood Institute (NHLBI) Intramural Research Program
- National Institutes of Health, NHLBI [4K22HL113069-02]
- College of Graduate Studies, University of the Sciences
- Department of Biological Sciences, University of the Sciences
Endothelial cells (ECs) migrate directionally during angiogenesis and wound healing by polarizing to extracellular cues to guide directional movement. EC polarization is controlled by microtubule (MT) growth dynamics, which are regulated by MT-associated proteins (MAPs) that alter MT stability. Mitotic centromere-associated kinesin (MCAK) is a MAP that promotes MT disassembly within the mitotic spindle, yet its function in regulating MT dynamics to promote EC polarity and migration has not been investigated. We used high-resolution fluorescence microscopy coupled with computational image analysis to elucidate the role of MCAK in regulating MT growth dynamics, morphology, and directional migration of ECs. Our results show that MCAK-mediated depolymerization of MTs is specifically targeted to the trailing edge of polarized wound-edge ECs. Regulation of MCAK function is dependent on Aurora A kinase, which is regionally enhanced by signaling from the small guanosine triphosphatase, Rac1. Thus, a Rac1-Aurora A-MCAK signaling pathway mediates EC polarization and directional migration by promoting regional differences in MT dynamics in the leading and trailing cell edges.
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