The Kinesin motor protein KIF5B regulates RNA trafficking and dendritic spine morphogenesis in hippocampal neuron

Abstract

Protein synthesis in neuron can occur locally near individual synapses of the postsynaptic neuron, which may serve to translate synaptic activity into the formation of persistent synaptic connections and mature dendritic spines. To achieve local protein synthesis, specific mRNAs must first be transported to the neuronal dendrites. The anterograde transport of selective cargoes, including mRNAs, protein complexes and organelles to distal dendrites, is carried out by the Kinesin Superfamily (KIFs) of molecular motors. Among them, the three members of the KIF5 family (KIF5A, KIF5B & KIF5C) are present in the ribonucleoprotein complexes (RNPs) that transport dendritic mRNAs. However, it is not clear whether individual KIF5 perform redundant or distinct functions in the transport of RNPs and the regulation of synapse structure. Here we performed time-lapse confocal imaging using the RNA dye SYTO 14 and the Mitotracker CMXRox to monitor the dynamics of RNPs in dissociated hippocampal neurons derived from wild-type or KIF5B heterozygous knockout mice. Consistent with previous studies, majority of the RNPs were stationary, and the motile RNPs exhibited discontinuous movement which was either oscillatory (bi-directional movement over short distances) or unidirectional (moving one direction over long distances). Interestingly, KIF5B heterozygous neurons contained significantly fewer stationary RNPs, and higher proportion of RNPs displayed unidirectional movement. We further found that knock down of KIF5B expression in rat hippocampal neurons using short hairpin RNA (shRNA) led to the loss of mature spines and a significant increase in the number of immature filopodia. These findings suggest that the kinesin KIF5B is crucial for the transport and docking of selective mRNAs, which may subsequently regulate the maturation of dendritic spines. This study was supported in part by the Research Grant Council of Hong Kong [General Research Fund (GRF) 16100814 and Early Career Scheme (ECS) 27119715].