TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation.
Bottom Line: TTBK2 depletion reduced MT lifetime (facilitated shrinkage and suppressed rescue) and impaired HeLa cell migration, and these phenotypes were partially restored by KIF2A co-depletion.Expression of nonphosphorylatable KIF2A, but not wild-type KIF2A, reduced MT lifetime and slowed down the cell migration.These findings indicate that TTBK2 with EB1/3 phosphorylates KIF2A and antagonizes KIF2A-induced depolymerization at MT plus ends for cell migration.
Affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.Show MeSH
Related in: MedlinePlus
License 1 - License 2
Mentions: Immunoblot analysis revealed that KIF2A was phosphorylated at S135 in HeLa cells (Fig. 2 E). When TTBK2 was depleted, the phosphorylation of KIF2A at S135 was reduced. The expression of TTBK2-WT in COS-7 cells increased the phosphorylation of exogenous or endogenous KIF2A at S135, whereas that of TTBK2–kinase inactive (KN) K50A (Bouskila et al., 2011) did not (Fig. 2 F and see Fig. 5 D). These results indicate that TTBK2 is responsible for the phosphorylation of KIF2A at S135 in intact cells and that KIF2A is a physiological substrate of TTBK2.
Affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.