DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration

Sci Rep. 2013:3:1681. doi: 10.1038/srep01681.


Cell motility and adhesion involve orchestrated interaction of microtubules (MTs) with their plus-end tracking proteins (+TIPs). However, the mechanisms underlying regulations of MT dynamics and directional cell migration are still elusive. Here, we show that DDA3-EB1 interaction orchestrates MT plus-end dynamics and facilitates directional cell migration. Biochemical characterizations reveal that DDA3 interacts with EB1 via its SxIP motif within the C-terminal Pro/Ser-rich region. Time-lapse and total internal reflection fluorescence (TIRF) microscopic assays demonstrate that DDA3 exhibits EB1-dependent, MT plus-end loading and tracking. The EB1-based loading of DDA3 is responsible for MT plus-ends stabilization at the cell cortex, which in turn orchestrates directional cell migration. Interestingly, the DDA3-EB1 interaction is potentially regulated by EB1 acetylation, which may account for physiological regulation underlying EGF-elicited cell migration. Thus, the EB1-based function of DDA3 links MT dynamics to directional cell migration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Movement / physiology*
  • HeLa Cells
  • Humans
  • Microtubules / physiology*
  • Molecular Motor Proteins / physiology*
  • Phosphoproteins / physiology*
  • Protein Binding


  • Molecular Motor Proteins
  • PSRC1 protein, human
  • Phosphoproteins