Characterizing Human KIF1Bß Motor Activity by Single-Molecule Motility Assays and Caenorhabtidis elegans Genetics
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Abstract
The 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 using Caenorhabditis elegans genetics. 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.
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To exclude the possibility that unc-104(Q94L) might be a gain-of-function allele and to confirm that unc-104(Q94L) is a hypomorphic allele, we crossed unc-104(Q94L) worms and unc-104(lf) to generate transheterozygotes, unc-104(Q94L)/unc-104(lf)
If unc-104(e1265) is a partial loss-of-function allele, is there a deletion, either gene-specific or chromosomal, that one can use to generate a true unc-104(Q94L)/unc-104(-) animal to test for a hypomorphic allele?
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Our results indicated that KIF1Bß(Q98L) was unable to rescue the body movement defects
I’m curious if you examined the expression levels of the mutant KIF1Bbeta protein? i.e. does the Q98L mutation alter protein expression levels?
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In this paper, we refer to this allele as unc-104(lf).
This is an elegant model to test the function of kinesins conserved across species! I just have a few questions. Is unc-104(e1265) a partial loss-of-function allele – a point mutation that demonstrates reduced PI(4,5)P(2) binding?
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