MOLECULAR MOTORS Who's Driving?

Kinesins are molecular motors that transport cargo such as proteins and membrane vesicles around the cell. In the case of a polarized cell like the neuron, kinesins ensure that cargo destined for axons or dendrites gets properly directed. However, just what "steers" these motors in the right direction is not clear. Setou et al. report that a binding protein of GluR2, one of the subunits of the dendritic -amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor, binds to the cargo-binding domain of the kinesin heavy chain. This binding protein, called glutamate-receptor-interacting protein (GRIP), colocalized with kinesin in dendritic shafts and soma of brain neurons. Kinesin also coimmunoprecipitated with GRIP and with GluR2 from dendrite-enriched subcellular brain fractions. Expression of the kinesin-binding domain of GRIP delocalized endogenous kinesin in somatodendritic regions but not in axons. A kinesin dominant negative mutant containing only the GRIP binding site reduced GRIP and GluR2 localization in synapses. Another scaffolding protein called c-Jun amino-terminal-kinase-interacting protein-1 (JIP) is known to bind to the kinesin light chain and is axon directed. Hence, traffic in neurons may be directed by categories of binding proteins that bring distinct motors and cargo together.

M. Setou, D.-H. Seog, Y. Tanaka, Y. Kanai, Y. Takei, M. Kawagishi, N. Hirokawa, Glutamate-receptor-interacting protein GRIP directly steers kinesin to dendrites. Nature 417, 83-87 (2002). [Online Journal]