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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Chew YL,Fan X,Götz J,Nicholas HRdoi
10.1242/jcs.jcs124404subject
Has Abstractpub_date
2013-05-01 00:00:00pages
2079-91issue
Pt 9eissn
0021-9533issn
1477-9137pii
jcs.jcs124404journal_volume
126pub_type
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