Signalling through the hedgehog (HH) pathway is crucial for cell proliferation and differentiation, and is aberrantly activated in a variety of cancers. The GLI proteins, of which there are three in mammals, are downstream effectors of HH signalling, and act in the nucleus to modulate HH target gene expression. Here (p. 1034), Brandon Carpenter and co-workers investigate the role of the kinesin-2 motor protein complex in the regulation of GLI proteins. They found that all three GLI proteins colocalized with the KAP3 subunit of kinesin-2 at the primary cilium, in the cytoplasm and in the nucleus, and that KAP3 directly interacted with the GLI proteins. They also showed that GLI2 interacted with another subunit of the kinesin-2 complex, KIF3A, but not with KIF3B, and that GLI2 could synergistically bind both KIF3A and KAP3A. The authors then mapped the interaction sites in these proteins and found that the interaction of GLI proteins with KAP3 had functional consequences for GLI protein activity. Specifically, the interaction had no effect on the transcriptional repressor form of GLI3, but it inhibited the transcriptional activator form of GLI2. Hence, these findings identify a direct role for the kinesin-2 motor protein complex in modulating HH signalling.

© 2015. Published by The Company of Biologists Ltd
2015