Abstract
Tauopathies include a broad range of neuropathological disorders that are based on defects in tau metabolisms. The microtubule-binding protein tau plays roles in Alzheimer’s disease in which tau accumulates in neurofibrillary tangles. In general, cargo accumulation (amyloid precursor protein, tau, neurofilaments) is a common observed phenomenon in degenerated neurons and it has been found that elevation of tau expression disrupts cargo transport, leading to cargo accumulation. Thus it seems to be important to investigate the interaction between microtubule-associated proteins and molecular motors. Here, we set out to investigate the interaction of tau/PTL-1 (Protein with Tau-Like repeats) and the major axonal transporter KIF1A/UNC-104 in Caenorhabditis elegans. In PTL-1 knock-out worms, the motility of UNC-104 is critically affected: more motor reversals for retrograde movements are observed and at the same time more pausing events for retrograde movements can be seen (compared to wildtype). Interestingly, similar behavior can be observed for UNC-104’s major cargo synaptobrevin-1 alone. Moreover, UNC-104 and PTL-1 co-localize and even co-migrate in the nervous system of living animals, suggesting that PTL-1 might be a cargo of UNC-104. Further motility analysis shows comparable fast transport rate of PTL-1. Last, we used bimolecular fluorescence complementation assay (BiFC) to test for interactions between PTL-1 and UNC-104 in the living worms. Indeed, using this novel assay (that can effortlessly replace the more complicated FLIM/FRET assay) we were able to identify interactions between these two proteins.