Role of CLASP2 in Microtubule Stabilization and the Regulation of Persistent Motility
In motile fibroblasts, stable microtubules (MTs) are oriented toward the leading edge of cells . How these polarized MT arrays are established and maintained, and the cellular processes they control, have been the subject of many investigations. Several MT "plus-end-tracking proteins," or +TIPs , have been proposed to regulate selective MT stabilization, including the CLASPs , a complex of CLIP-170, IQGAP1, activated Cdc42 or Rac1 , a complex of APC, EB1, and mDia1 , and the actin-MT crosslinking factor ACF7 . By using mouse embryonic fibroblasts (MEFs) in a wound-healing assay, we show here that CLASP2 is required for the formation of a stable, polarized MT array but that CLIP-170 and an APC-EB1 interaction are not essential. Persistent motility is also hampered in CLASP2-deficient MEFs. We find that ACF7 regulates cortical CLASP localization in HeLa cells, indicating it acts upstream of CLASP2. Fluorescence-based approaches show that GFP-CLASP2 is immobilized in a bimodal manner in regions near cell edges. Our results suggest that the regional immobilization of CLASP2 allows MT stabilization and promotes directionally persistent motility in fibroblasts.
|Persistent URL||dx.doi.org/10.1016/j.cub.2006.09.065, hdl.handle.net/1765/59476|
Drabek, K, van Ham, M, Stepanova, T, Draegestein, K, van Horssen, R, Sayas, C.L, … Galjart, N.J. (2006). Role of CLASP2 in Microtubule Stabilization and the Regulation of Persistent Motility. Current Biology, 16(22), 2259–2264. doi:10.1016/j.cub.2006.09.065