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Live‐cell single‐molecule imaging reveals clathrin and caveolin‐1 dependent docking of SMAD4 at the cell membrane
Author(s) -
Yang Yong,
Wolfram Joy,
Shen Jianliang,
Zhao Yuliang,
Fang Xiaohong,
Shen Haifa,
Ferrari Mauro
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.10.041
Subject(s) - microbiology and biotechnology , cell signaling , effector , docking (animal) , clathrin , cell , cytoplasm , cell membrane , live cell imaging , signal transduction , chemistry , total internal reflection fluorescence microscope , biology , membrane , endocytosis , biochemistry , medicine , nursing
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.