Building a highly polarized cell requires the specific transport of proteins to their final destinations. Kinesin and its binding proteins can direct this differential transport in neuronal cells, according to new results from Mitsutoshi Setou, Nobutaka Hirokawa (University of Tokyo, Tokyo, Japan), and colleagues.
Kinesin can transport vesicles along microtubules to the axon by binding to the scaffolding protein JSAP1. But now it appears that the motor is not always partial to the axon. Using the glutamate receptor subunit GluR2 as cargo, Hirokawa's group demonstrated that kinesin could also transport its cargo to dendrites, where the receptors are required.
Upon this discovery, Hirokawa says, “we were then interested in understanding how the same motor could determine the direction of transport.” They found their answer in a screen for kinesin binding partners, which identified a glutamate receptor–interacting protein, GRIP-1. Whereas kinesin bound to GRIP-1 was recruited to dendrites, kinesin bound to JSAP1 moved to axons. It is thus the scaffolding proteins that direct kinesin and its cargo toward their destination.
Previously identified scaffolding proteins, such as JSAP1, have shown a preference for binding to kinesin light chain. Hirokawa points out that fungal kinesin lacks a light chain but still transports cargo. Sure enough, GRIP-1 binds the heavy chain. Thus, the choice of subunit bound may be important in determining the direction kinesin travels. ▪