p(HBP:"Tau isoform F (441 aa)")

Entity

Name

Tau isoform F (441 aa)

Namespace

HBP

Namespace Version

20181023

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/3074b85b858455d8eeb76cfcdef685ced19bbe11/export/hbp-names.belns

As expected, we observed a significant impairment of mitochondrial distribution with overexpression of all three tau constructs (p < 0.0001, Wilcoxon test for GFP control versus 4R-tau, GFP versus tauC3, and GFP versus K18ΔK280) (Fig. 5). PubMed:25374103

Taken together, these data indicate that tau-overexpression leads to abnormal mitochondrial trafficking that can be rescued by CHIP-co-expression PubMed:25374103

Interestingly, a significant decrease in tau levels was seen with the co-transfection of CHIPΔU (U-box deleted) when transfected with either K18ΔK280 or 4R-Tau. PubMed:25374103

Densitometry analysis of total tau levels of H4- cell lysates on SDS-PAGE showed a 2.0 to 2.5 fold lower levels of tau (4R-tau, tauC3, and K18ΔK280) with co-expression with CHIP, respectively (Fig. 1). PubMed:25374103

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

Indeed, knockdown of FUS increases the expression of the 2N and 4R tau isoforms, providing a possible link between frontotemporal lobar degeneration-FUS (FTLDFUS; a subtype of FTD characterized by FUS inclusions in neurons and glia) and FTLD-tau (a tauopathy). PubMed:26631930

Comparison of the mitochondrial transport in the wildtype tau and TauA152T lines revealed striking differences; wild-type tau lines showed a late onset akin to both antero- and retrograde mitochondrial transport defects, whereas TauA152T lines showed mainly early-onset anterograde mitochondrial transport defects PubMed:29191965

Comparison of the mitochondrial transport in the wildtype tau and TauA152T lines revealed striking differences; wild-type tau lines showed a late onset akin to both antero- and retrograde mitochondrial transport defects, whereas TauA152T lines showed mainly early-onset anterograde mitochondrial transport defects PubMed:29191965

Toxicity assays revealed that neither CHIP nor any of the tau constructs caused cell death compared to the control GFP vector (Supplementary Fig. 1). PubMed:25374103

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

As expected, we observed a significant impairment of mitochondrial distribution with overexpression of all three tau constructs (p < 0.0001, Wilcoxon test for GFP control versus 4R-tau, GFP versus tauC3, and GFP versus K18ΔK280) (Fig. 5). PubMed:25374103

Taken together, these data indicate that tau-overexpression leads to abnormal mitochondrial trafficking that can be rescued by CHIP-co-expression PubMed:25374103