Kinesin I motor proteins KIF5A and KIF5B play non-redundant roles on excitatory synapse development

Abstract

Aims: Spine maturation is regulated by an extensive repertoire of dendritic proteins, which highly depend on well-organized transport from the cell body to dendrites. Kinesins are motor proteins which transport multiple cargoes to both axons and dendrites along microtubules. Kinesin 1 family, which consists of three highly homologous members (KIF5A, KIF5B and KIF5C), was reported to transport glutamate-receptor-interacting-protein to dendrites directly. Glutamate receptors play a necessary role in mediating fast excitatory synaptic transmission between neurons and mainly concentrated on the heads of mature spines. Whether KIF5A, KIF5B and KIF5C have non-overlapping roles in regulating the development and function of excitatory synapses remains unexplored. Our study aims to identify the function of individual KIF5s on spine maturation and excitatory synaptic transmission between neurons. Methods: To determine the roles of individual KIF5s on spine maturation, we designed specific short hairpin RNAs (shRNAs) to knock down KIF5s in cultured hippocampal neurons. Confocal imaging and whole-cell patch clamp were then conducted for spine morphology detection and miniature excitatory postsynaptic currents (mEPSCs) recording. Results: The knock-down of KIF5B, but not KIF5A, lead to decreased mushroom spines and reduced mEPSC frequency. Conclusions: Our study demonstrates that individual KIF5 motor protein has unique and non-redundant roles in regulating the function of excitatory synapses.