title: Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor's motility characteristics in C. elegans neurons.
abstract: 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.
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, 30013 Hsinchu, Taiwan, ROC.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tien
authors.forename: Gong-Her
authors.initials: GH
authors.lastname: Wu
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Hsu
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chang
authors.forename: Oliver I
authors.initials: OI
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics* / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology; D020409:Molecular Motor Proteins / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
chemical_list: D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; C100857:PTL-1 protein, C elegans; C423186:UNC-104 protein, C elegans