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

Chew, Yee Lian, Fan, Xiaochen, Gotz, Jurgen and Nicholas, Hannah R. (2014) Regulation of age-related structural integrity in neurons by protein with tau-like repeats (PTL-1) is cell autonomous. Scientific Reports, 4 . doi:10.1038/srep05185


Author Chew, Yee Lian
Fan, Xiaochen
Gotz, Jurgen
Nicholas, Hannah R.
Title Regulation of age-related structural integrity in neurons by protein with tau-like repeats (PTL-1) is cell autonomous
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2014-06-05
Year available 2014
Sub-type Article (original research)
DOI 10.1038/srep05185
Open Access Status DOI
Volume 4
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Groups
Language eng
Formatted 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID P40 OD010440
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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Created: Tue, 24 Jun 2014, 10:27:33 EST by System User on behalf of Clem Jones Centre for Ageing Dementia Research