Elucidating the non-redundant role of different Kinesin 1 motor proteins in dendritic mRNA transport of neuron

Abstract

RNA transport is a key component of the local protein synthesis machinery in neurons, and Kinesin 1 (KIF5A, B and C) is the conventional kinesin that has been linked to this process. However, it is unknown whether three Kinesin I homologs have specific roles in RNA transport. In this study, we aim to investigate how specific depletion of KIF5B disrupts the dendritic RNA transport and trafficking of the RNA-binding protein FMRP. Our results demonstrated that both KIF5A and KIF5B may regulate FMRP transport in hippocampal neurons but in different manners. KIF5B has a general effect on total granule density, while reduction of KIF5A upregulates oscillatory and retrograde granule density. This indicates that KIF5A may have a role on the docking and stabilization of FMRP granules. The observations of RNP granules in kif5b+/- neurons showed significantly fewer stationary RNPs, and higher proportion of the RNPs of unidirectional movement. Our results call for further investigation on mechanisms by which KIF5A and KIF5B may differentially regulate RNP movement is to be conducted and specific RNA cargos are to be identified.