title: Regulation of age-related structural integrity in neurons by protein with tau-like repeats (PTL-1) is cell autonomous.
abstract: PTL-1 is the sole homolog of the MAP2/MAP4/tau family in Caenorhabditis elegans. Accumulation of tau is a pathological hallmark of neurodegenerative diseases such as Alzheimer's disease. Therefore, reducing tau levels has been suggested as a therapeutic strategy. We previously showed that PTL-1 maintains age-related structural integrity in neurons, implying that excessive reduction in the levels of a tau-like protein is detrimental. Here, we demonstrate that the regulation of neuronal ageing by PTL-1 occurs via a cell-autonomous mechanism. We re-expressed PTL-1 in a null mutant background using a pan-neuronal promoter to show that PTL-1 functions in neurons to maintain structural integrity. We next expressed PTL-1 only in touch neurons and showed rescue of the neuronal ageing phenotype of ptl-1 mutant animals in these neurons but not in another neuronal subset, the ventral nerve cord GABAergic neurons. Knockdown of PTL-1 in touch neurons also resulted in premature neuronal ageing in these neurons but not in GABAergic neurons. Additionally, expression of PTL-1 in touch neurons alone was unable to rescue the shortened lifespan observed in ptl-1 mutants, but pan-neuronal re-expression restored wild-type longevity, indicating that, at least for a specific group of mechanosensory neurons, premature neuronal ageing and organismal ageing can be decoupled.
authors.affiliation: 1] School of Molecular Bioscience, University of Sydney, Australia [2].
authors.forename: Yee Lian
authors.initials: YL
authors.lastname: Chew
authors.affiliation: 1] School of Molecular Bioscience, University of Sydney, Australia [2].
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Fan
authors.affiliation: Clem Jones Centre for Ageing Dementia Research (CJCADR) at the Queensland Brain Institute (QBI), University of Queensland, Australia.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.affiliation: School of Molecular Bioscience, University of Sydney, Australia.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Nicholas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D008136:Longevity / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; C100857:PTL-1 protein, C elegans