| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3069673 | Neurobiology of Disease | 2011 | 12 Pages |
Tauopathies are neurodegenerative diseases based on pathological tau-aggregation including Alzheimer's disease, frontotemporal dementia (FTD) and Pick's disease. In general, cargo (e.g., β-amyloid precursor protein, tau, neurofilaments) accumulation is a commonly observed phenomenon in degenerated neurons. Therefore, it is crucial to investigate the interaction between cargo, microtubule-binding proteins and molecular motors. We report the effect of tau/PTL-1 (protein with tau-like repeats) on the transport characteristics of the major axonal transporter kinesin-3 KIF1A/UNC-104 in the nervous system of Caenorhabditis elegans. Using confocal spinning disk time-lapse imaging we analyzed the motility of UNC-104::mRFP in ptl-1 knockout worms and found that predominantly retrograde moving characteristics are affected (rather than the motor's anterograde displacements). A similar motility pattern was observed for synaptobrevin-1-containing vesicles, a major cargo of UNC-104. Moreover, UNC-104 and PTL-1 colocalize and occasionally co-migrate. We further confirmed physical interactions between PTL-1 and UNC-104 in living animals using the bimolecular fluorescence complementation assay (BiFC) as well as in co-immunoprecipitation experiments. Though this study focuses on PTL-1/UNC-104 interactions, we extended our research on monitoring conventional kinesin-1 (UNC-116) as well as dynein motility pattern and found that in ptl-1 mutants retrograde displacements were also affected for UNC-116, while for dynein, interestingly, its anterograde movements were affected.
Research highlights► KIF1A/UNC-104 physically interacts and co-migrates with tau/PTL-1 in C. elegans. ► Tau/PTL-1 knockout affects UNC-104's retrograde movements, but not its anterograde motility. ► Similar effects of tau/PTL-1 knockout was found on motility of synaptic vesicles alone and kinesin-1/UNC-116. ► The effect on dynein is vice versa: retrograde motility was not affected but the motor's anterograde movements.
