Regulation of Focal Adhesion Dynamics and Cell Motility by EB2 and Hax1 Complex [Signal Transduction]

November 2nd, 2015 by Liu, H., Yue, J., Huang, H., Gou, X., Chen, S.-Y., Zhao, Y., Wu, X.

Cell migration is a fundamental cellular process, requiring integrated activities of cytoskeleton, membrane, and cell/ECM 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; while in contrast, EB2 does not play a direct role in microtubule dynamic instability, and little is known about EB2 cellular function. By quantitative proteomics, we identified mammalian HAX1 (HCLS1 associated protein X-1), which associates with EB2 specifically. 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 requires 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.