The specific role of the motor protein KIF5B in dendritic transport, synaptic plasticity and memory

Kinesin and dynein are microtubule-dependent molecular motors that mediate long distance transport of molecules and organelles in neuron. The kinesin superfamily is very diverse and contains 45 members in mammal. One key question that is not well addressed is whether and how the different kinesin motors exhibit transport specificity that underlie distinct neuronal functions such as synapse development and plasticity. While there is only one kinesin I protein in the invertebrates, gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in the vertebrates. These homologs were initially regarded as functionally redundant because of their conserved cargo-binding domains. Here we show that conditional knockout mice which specifically lack KIF5B in excitatory neurons after birth display defects in dendritic spine morphogenesis and plasticity, which are coupled with impaired long-term potentiation and memory formation. Notably, using specific shRNAs to acutely knock down individual KIF5s, we found that KIF5B but not the closely related KIF5A has a specific function for excitatory synapse formation and dendritic transport of the RNA-binding protein FMRP. The functional specificity is conferred by their highly diverse short carboxyl-tails at the proximity of the cargo-binding domain. Furthermore, the carboxyl-tail of KIF5B might undergo posttranslational modification that regulates cargo binding. We are currently investigating the potential role of KIF5B in mRNA trafficking to the sub-dendritic compartments of neurons.