TC10 (green) colocalizes with caveolin (red) to signal.

On page 829, Watson et al. find that the small GTP-binding protein TC10 must be in a lipid raft compartment to impact insulin signaling. Such spatial control may be one way in which cells create a distinct reponse from activation of a common set of signal transduction proteins.

Insulin acts on the insulin receptor to trigger translocation of the GLUT4 transporter to the plasma membrane, resulting in increased glucose uptake. In previous studies, activation of both PI 3-kinase and TC10 were implicated in transducing a signal from activated receptor to GLUT4.

Now Watson et al. show that TC10 localizes to lipid raft domains, and that inhibition of this localization (using a dominant-interfering caveolin mutant) prevents TC10 activation by insulin. Although the current authors and others have worked out a complex series of links from the activated receptor to TC10, it seems that these links can only be set up productively when the relevant proteins are concentrated in a specific domain. ▪