title: Regulation of Focal Adhesion Dynamics and Cell Motility by the EB2 and Hax1 Protein Complex.
abstract: Cell migration is a fundamental cellular process requiring integrated activities of the cytoskeleton, membrane, and cell/extracellular matrix adhesions. Many cytoskeletal activities rely on microtubule filaments. It has been speculated that microtubules can serve as tracks to deliver proteins essential for focal adhesion turnover. Three microtubule end-binding proteins (EB1, EB2, and EB3) in mammalian cells can track the plus ends of growing microtubules. EB1 and EB3 together can regulate microtubule dynamics by promoting microtubule growth and suppressing catastrophe, whereas, in contrast, EB2 does not play a direct role in microtubule dynamic instability, and little is known about the cellular function of EB2. By quantitative proteomics, we identified mammalian HCLS1-associated protein X-1 (HAX1) as an EB2-specific interacting protein. Knockdown of HAX1 and EB2 in skin epidermal cells stabilizes focal adhesions and impairs epidermal migration in vitro and in vivo. Our results further demonstrate that cell motility and focal adhesion turnover require interaction between Hax1 and EB2. Together, our findings provide new insights for this critical cellular process, suggesting that EB2 association with Hax1 plays a significant role in focal adhesion turnover and epidermal migration.
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yue
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Gou
authors.affiliation: the Department of Pharmacology and Toxicology, University of Louisville Health Science Center, Louisville, Kentucky, 40292.
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: From the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637 and xiaoyangwu@uchicago.edu.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000607391:EB2 protein, mouse; C491295:Hs1bp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins
keywords: Hax1; cell migration; cell signaling; focal adhesion; microtubule; plus ends; proteomics