By: Richard Liang 18’ 

Insulin is an important signaling factor in glucose uptake, acting in concert with glucose transporter GLUT4 to transport glucose into skeletal muscle and adipose tissue. In the presence of insulin, GLUT4 is translocated to the plasma membrane where an exocyst complex tethers the GLUT4 to the membrane, a process that requires G protein RalA to bind to the resulting complex. However, not much is known bout the mechanism of RaIA after activation. In a study led by Maeran Uhm from the Life Science Institute in the University of Michigan, the process following the activation of RaIA was investigated.

The protein kinase TBK1 was discovered to act as a “gatekeeper” in controlling GLUT4 vesicle engagement and disengagement from the exocyst complex, thereby regulating insulin-stimulated glucose transport. When RaIA was activated, TBK1 phosphorylated the exocyst subunit Exo84, allowing glucose uptake to occur in cells. Using immunoblots, it was observed that the knockdown of TBK1 inhibited insulin stimulated glucose uptake and GLUT4 translocation, indicating its role in maintaining the exocyst complex. However, overexpression of a kinase-inactive mutant variant of TBK1 reduced insulin-stimulate glucose uptake as well as preventing the complex from dissociating. The data indicated that TBK1 was also involved in controlling vesicle fusion at the plasma membrane.

The researchers note that although it is not unprecedented that protein kinase is involved in anabolic operations akin to glucose uptake, it is unusual and merits further investigation. Continuing research on this topic could lead to increased understanding of the intricate mechanisms of the factors that influence glucose transport.

References

1. Uhm, et al., Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking. Science Signaling 10, (2017). DOI: 10.1126/scisignal.aah5085

Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/thumb/5/57/Human-insulin-hexamer-3D-ribbons.png/614px-Human-insulin-hexamer-3D-ribbons.png