The intracellular transport of NMDA receptors is one of the prerequisites for NMDA receptor activity. Hirokawa's group previously reported that KIF17 is a candidate transporter of NR2B. However, the precise role of KIF17 in vivo has remained obscure. Hirokawa's group analyzed newly generated knockout mice carrying a targeted mutation in the kif17 gene, and found that the levels of both NR2B and NR2A were significantly reduced in kif17^−/− mouse synapses (Fig. 1). It is further demonstrated that KIF17 differentially maintains levels of synaptic NR2A and NR2B subunits in vivo. In kif17^+/+ mouse neurons, synaptic inputs upregulate NR2B and KIF17 through CREB activity. The increase in the levels of KIF17 and NR2B leads to increased transport and synaptic accumulation of NR2B. Conversely, in kif17^−/− neurons, failure of the reciprocal regulation between KIF17/NR2B and CREB, as well as the accelerated degradation of NR2A mediated by the ubiquitin–proteasome system, resulted in memory disturbances found in kif17^−/− mice. These findings should open the door to strategies for treatment of learning deficits and mental disorders in the future.

Program member
Nobutaka Hirokawa (Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo)

Fig. 1