Fig. 9. Models for activity-dependent local transport regulatory mechanisms via local degradation and synthesis of KIF17, leading to regulation of NR2B deposition.

Models for the molecular mechanisms of local KIF17 degradation and synthesis. (A) Model for the molecular mechanism of local KIF17 degradation. (A1) KIF17 unloads NR2B in response to Ca²⁺ influx through NMDAR activation. (A2) KIF17 is polyubiquitinated in an activity-dependent manner. (A3) The proteasome proteolyzes polyubiquitinated KIF17. (B) Model for the molecular mechanism of local KIF17 synthesis. (B1) PAIP2A is degraded by calpain in the NMDAR-mediated pathway, leading to augmented binding of poly(A)-binding protein (PABP) to Kif17 mRNA. (B2) PABP binding to Kif17 mRNA facilitates translation initiation. (B3) Kif17 mRNA is locally translated at the dendritic shaft. (B4) Newly synthesized KIF17 participates in cargo transport along microtubules, suggesting the regulation of local deposition of NR2B along a dendritic shaft that is crucial for cognitive flexibility.