title: The Microtubule Plus End Tracking Protein TIP150 Interacts with Cortactin to Steer Directional Cell Migration.
abstract: Cell migration is orchestrated by dynamic interactions of microtubules with the plasma membrane cortex. How these interactions facilitate these dynamic processes is still being actively investigated. TIP150 is a newly characterized microtubule plus end tracking protein essential for mitosis and entosis (Ward, T., Wang, M., Liu, X., Wang, Z., Xia, P., Chu, Y., Wang, X., Liu, L., Jiang, K., Yu, H., Yan, M., Wang, J., Hill, D. L., Huang, Y., Zhu, T., and Yao, X. (2013) Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis. J. Biol. Chem. 288, 15771-15785; Xia, P., Zhou, J., Song, X., Wu, B., Liu, X., Li, D., Zhang, S., Wang, Z., Yu, H., Ward, T., Zhang, J., Li, Y., Wang, X., Chen, Y., Guo, Z., and Yao, X. (2014) Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction. J. Mol. Cell Biol. 6, 240-254). Here we show that TIP150 links dynamic microtubules to steer cell migration by interacting with cortactin. Mechanistically, TIP150 binds to cortactin via its C-terminal tail. Interestingly, the C-terminal TIP150 proline-rich region (CT150) binds to the Src homology 3 domain of cortactin specifically, and such an interaction is negatively regulated by EGF-elicited tyrosine phosphorylation of cortactin. Importantly, suppression of TIP150 or overexpression of phospho-mimicking cortactin inhibits polarized cell migration. In addition, CT150 disrupts the biochemical interaction between TIP150 and cortactin in vitro, and perturbation of the TIP150-cortactin interaction in vivo using a membrane-permeable TAT-CT150 peptide results in an inhibition of directional cell migration. We reason that a dynamic TIP150-cortactin interaction orchestrates directional cell migration via coupling dynamic microtubule plus ends to the cortical cytoskeleton.
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and.
authors.forename: Gregory
authors.initials: G
authors.lastname: Adams
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wu
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Quan
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Jiang
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mo
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Medicine and Neurobiology, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Kelwyn
authors.initials: K
authors.lastname: Thomas
authors.affiliation: the Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama 35294, and.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Hill
authors.affiliation: Medicine and Neurobiology, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Felix O
authors.initials: FO
authors.lastname: Aikhionbare
authors.affiliation: the Departments of Physiology and the Guangzhou Women and Children's Medical Center, Guangzhou 510623, China heping-2008@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, the Departments of Physiology and xing1017@ustc.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the BUCM-MSM Joint Research Group for Cellular Dynamics, BUCM School of Basic Medical Sciences, and Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, Anhui 230026, China, dingx@bucm.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: the Departments of Physiology and.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D018909:src Homology Domains
chemical_list: C495868:CTTN protein, human; D051356:Cortactin; C546899:MTUS2 protein, human; D008869:Microtubule-Associated Proteins
keywords: cell invasion; cell migration; cell motility; cellular regulation; microtubule; microtubule-associated protein (MAP)