Regulation of age-related structural integrity in neurons by protein with tau-like repeats (PTL-1) is cell autonomous

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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Article number5185
Number of pages9
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 5 Jun 2014
Externally publishedYes

Keywords

  • Cell biology
  • Neuroscience
  • Caenorhabditis elegans
  • Alzheimer's disease
  • Accumulation of tau
  • age-related structural integrity
  • PTL-1
  • premature neuronal ageing
  • GABAergic neurons

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