Kinesin I proteins regulate the RNA binding protein FMRP in hippocampal neurons

Abstract

Aims: Kinesin 1 (KIF5A, B and C) has been linked to RNA transport in neuronal dendrites, which is critical to local protein synthesis and synaptic plasticity. Given our previous findings that knockdown of KIF5A and KIF5Bproduce different effects on the development of excitatory synapses and synaptic transmission in hippocampal neurons, we aim to further investigate whether depletion of the two kinesin proteins differentially regulate the dendritic transport of RNA and the RNA-binding protein FMRP. Methods: To investigate FMRP expression and motility, KIF5B or KIF5A was knocked down using specific shRNAs in rat hippocampal neurons, and immunostaining by FMRP antibody or live imaging of GFP-FMRP was performed. To understand if the mRNA transport were affected by KIF5B depletion in vivo, the abundance of selected FMRP targets from synaptoneurosome fractions of CaMKIIα-Cre;Kif5bfl/fl conditional knockout mice was quantified using qPCR. Results: Knockdown of KIF5B but not KIF5A show differential effects on FMRP expression and motility. Differential expression in specific mRNAs that are FMRP targets were observed in the synaptoneurosome of the KIF5B conditional knockout mice. Conclusions: KIF5 proteins can differentially regulate FMRP expression and/or motility, and specific synaptic transcripts are regulated by KIF5B in vivo.