Characterizing Human KIF1Bß Motor Activity by Single-Molecule Motility Assays andCaenorhabtidis elegansGenetics

Abstract

AbstractThe axonal transport of synaptic vesicle precursors relies on KIF1A and UNC-104 ortholog motors. In mammals, KIF1Bß is also responsible for the axonal transport of synaptic vesicle precursors. Mutations in KIF1A and KIF1Bß lead to a wide range of neuropathies. While previous studies have revealed the biochemical, biophysical and cell biological properties of KIF1A, and its defects in neurological disorders, the fundamental properties of KIF1Bß remain elusive. In this study, we determined the motile parameters of KIF1Bß through single-molecule motility assays. Additionally, we established simple methods for testing the axonal transport activity of human KIF1Bß usingCaenorhabditis elegansgenetics. Taking advantage of these methods, we demonstrated that these assays enable the detection of reduced KIF1Bß activities both in vitro and in vivo, that is caused by a disease-associated mutation.