Live-cell single-molecule imaging reveals clathrin and caveolin-1 dependent docking of SMAD4 at the cell membrane Academic Article uri icon


MeSH Major

  • Caveolin 1
  • Cell Membrane
  • Clathrin
  • Smad4 Protein


  • Transforming growth factor β (TGF-β) signaling is important for many biological processes. Although the sequential events of this cascade are known, the dynamics remain speculative. Here, live-cell single-molecule total internal reflection fluorescence microscopy was used to monitor the dynamics of SMAD4, a TGF-β downstream effector, in MDA-MB-231 breast cancer cells. Contrary to previous belief, SMAD4 was detectable at the cytoplasmic membrane, displaying two subpopulations with different membrane docking behaviors. These subpopulations were regulated by clathrin and caveolin-1, and had opposing roles in the nuclear shuttling of SMAD4 and the subsequent transcriptional regulation of genes associated with cell migration. The notion that membrane-docking behaviors of downstream molecules could predict the cellular response to growth factors may revolutionize the way we view cell signaling.

publication date

  • December 11, 2013



  • Academic Article



  • eng

PubMed Central ID

  • PMC3903459

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2013.10.041

PubMed ID

  • 24211445

Additional Document Info

start page

  • 3912

end page

  • 20


  • 587


  • 24