PTL-1 regulates neuronal integrity and lifespan in C. elegans

Yee Lian Chew, Xiaochen Fan, Jürgen Götz, Hannah R. Nicholas

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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 axonand 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 taufunction and not solely from a toxic gain-of-function due to accumulation of tau.

Original languageEnglish
Pages (from-to)2079-2091
Number of pages13
JournalJournal of Cell Science
Volume126
Issue number9
DOIs
Publication statusPublished - May 2013
Externally publishedYes

Keywords

  • Aging
  • Alzheimer's disease
  • Caenorhabditis elegans
  • Neurodegenerative diseases
  • Protein with tau-like repeats
  • PTL-1
  • Tau

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