The Molecular Motor Protein Kif5C Mediates Structural Plasticity and Long-Term Memory by Constraining Local Translation

Synaptic structural plasticity, a key component of long-term memory storage, requires translation of localized RNAs delivered by long-distance transport from the neuronal cell body. However,the mechanisms and regulation of this transport process that ensures structural plasticity remain elusive. Here,we explored the roles of Kif5C and Kif3A, two members of the Kinesin superfamily of transport machinery (Kifs), and foundthat loss of function of either onedecreased structural plasticity,whereas gain of function of Kif5C enhanced it. Importantly, Kif5C function is a rate-determining component of local translation and mediates the transport of ~650 RNAs, including EIF3G, a regulator of translation initiation, and plasticity-associated RNAs. Additionally, loss of function of Kif5C in dorsal hippocampal CA1 neurons constrained both spatial and contextual fear memory,whereas its gain of function specifically enhanced spatial memory. Therefore, Kif5C-mediated long-distance transport of substrates of synaptic translation is a key mechanism underlying structural plasticity and memory.