Motoring to a signaling check-up

The Smad2 signaling protein is shuttled back to the membrane to check up on its receptor, according to Julie Batut, Michael Howell and Caroline Hill (Cancer Research UK, London). The check-ups ensure that intracellular signaling accurately reflects the activation status of the membrane-bound receptor.

Smad proteins are phosphorylated by and act downstream of TGF-β receptors. Once Smad2 has helped activate transcription, the group previously found, it is shuttled out of the nucleus.

They now discover that this discarded Smad2 is dragged back to the TGF-β receptor by the microtubule motor kinesin. Smad2 phosphorylation and nuclear accumulation was prevented by microtubule poisons and an antikinesin drug, even in the presence of a constitutively activated receptor. This result held true in frog and zebrafish embryos and mammalian cells. Unphosphorylated Smad2 coimmunoprecipitated with a kinesin light chain.

Long-range transport of Smad2...