title: PTL-1 regulates neuronal integrity and lifespan in C. elegans.
abstract: Protein with tau-like repeats (PTL-1) is the sole Caenorhabditis elegans homolog of tau and MAP2, which are members of the mammalian family of microtubule-associated proteins (MAPs). In mammalian neurons, tau and MAP2 are segregated, with tau being mainly localised to the axon and MAP2 mainly to the dendrite. In particular, tau plays a crucial role in pathology, as elevated levels lead to the formation of tau aggregates in many neurodegenerative conditions including Alzheimer's disease. We used PTL-1 in C. elegans to model the biological functions of a tau-like protein without the complication of functional redundancy that is observed among the mammalian MAPs. Our findings indicate that PTL-1 is important for the maintenance of neuronal health as animals age, as well as in the regulation of whole organism lifespan. In addition, gene dosage of PTL-1 is crucial because variations from wild-type levels are detrimental. We also observed that human tau is unable to robustly compensate for loss of PTL-1, although phenotypes observed in tau transgenic worms are dependent on the presence of endogenous PTL-1. Our data suggest that some of the effects of tau pathology result from the loss of physiological tau function and not solely from a toxic gain-of-function due to accumulation of tau.
authors.affiliation: School of Molecular Bioscience, University of Sydney, New South Wales, 2006, Australia.
authors.forename: Yee Lian
authors.initials: YL
authors.lastname: Chew
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Fan
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Nicholas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D008136:Longevity / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; C100857:PTL-1 protein, C elegans; D016875:tau Proteins
keywords: Aging; Alzheimer's disease; Caenorhabditis elegans; Neurodegenerative diseases; PTL-1; Protein with tau-like repeats; Tau