Editors' ChoiceCell Biology

Smads on the Move

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Science's STKE  24 Aug 2004:
Vol. 2004, Issue 247, pp. tw302
DOI: 10.1126/stke.2472004tw302

The general scheme by which transforming growth factor β (TGF-β) receptors signal to the nucleus is one in which activated receptors cause phosphorylation and activation of Smad proteins, which then accumulate in the nucleus. However, closer inspection reveals that the dynamic behavior of Smad proteins is somewhat more complicated. Nicolás et al. made Smad fusion proteins with green fluorescent protein and monitored movement of the proteins in live cells in FLIP (fluorescence loss in photobleaching) experiments. The results show that although most GFPSmad4 is in the cytoplasm of unstimulated cells, the protein does rapidly shuttle between the cytoplasm and the nucleus. Distinctions could be made between the different Smads, and GFPSmad2 was less mobile in the cytoplasm than was GFPSmad4, indicating that interactions with other molecules may tether Smad 2 in the cytoplasm. Using a combination of FLIP and FRAP (fluorescence recovery after photobleaching), the authors found that after stimulation of cells with TGF-β, both Smads showed reduced mobility in the nucleus, which presumably results from interactions that hold the activated proteins in the nucleus. It will now be of interest to determine the precise nature of the interactions that modulate shuttling of Smads between the cytoplasm and the nucleus.

F. J. Nicolás, K. De Bosscher, B. Schmierer, C. S. Hill, Analysis of Smad nucleocytoplasmic shuttling in living cells. J. Cell Sci., 117, 4113-4125 (2004). [Abstract] [Full Text]

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