title: Rac1 and Aurora A regulate MCAK to polarize microtubule growth in migrating endothelial cells.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104.
authors.forename: Alexander
authors.initials: A
authors.lastname: Braun
authors.affiliation: Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104.
authors.forename: Kyvan
authors.initials: K
authors.lastname: Dang
authors.affiliation: Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104.
authors.forename: Felinah
authors.initials: F
authors.lastname: Buslig
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, The Florida State University, Tallahassee, FL 32310 National High Magnetic Field Laboratory and Department of Biological Science, The Florida State University, Tallahassee, FL 32310.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, The Florida State University, Tallahassee, FL 32310 National High Magnetic Field Laboratory and Department of Biological Science, The Florida State University, Tallahassee, FL 32310.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 k.myers@usciences.edu watermancm@nhlbi.nih.gov.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Waterman
authors.affiliation: Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104 Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 k.myers@usciences.edu watermancm@nhlbi.nih.gov.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Myers
mesh_terms: D064096:Aurora Kinase A / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D021381:Protein Transport; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C091489:KIF2C protein, human; C107953:RAC1 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; D016547:Kinesins; D020830:rac1 GTP-Binding Protein