Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-α) in C. elegans neurons.

The accumulation of cargo (tau, amyloid precursor protein, neurofilaments etc.) in neurons is a hallmark of various neurodegenerative diseases while we have only little knowledge how axonal transport is regulated. Kinesin-3 UNC-104(KIF1A) is the major transporter of synaptic vesicles and recent reports suggest that a cargo itself can affect the motor's activity. Inspecting an interactome map, we identify three putative UNC-104 interactors, namely UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-α), known to be adaptors in essential neuronal protein complexes. We then employed the novel method bimolecular fluorescence complementation (BiFC) assay to visualize motor-adaptor complexes in the nervous system of living C. elegans. Interestingly, the binding of UNC-104 to each adaptor protein results in different sub-cellular distributions and has distinctive effects on the motor's motility. Specifically, if UNC-104 bound to UNC-16, the motor is primarily localized in the soma of neurons while bound to DNC-1, the motor is basically found in axonal termini. On the other hand, if UNC-104 is bound to SYD-2 we identify motor populations mostly along axons. Therefore, these three adaptors inherit different functions in steering the motor to specific sub-cellular locations in the neuron.