Equivalencies: 1 | Classes: 0 | Children: 0 | Explore

Appears in Networks 3

In-Edges 4

p(HBP:"VQIINK motif") positiveCorrelation p(HGNC:MAPT, var("p.Lys280del")) View Subject | View Object

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

Appears in Networks:

p(HBP:"VQIVYK motif") positiveCorrelation p(HGNC:MAPT, var("p.Lys280del")) View Subject | View Object

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

Appears in Networks:

Out-Edges 23

p(HGNC:MAPT, var("p.Lys280del")) positiveCorrelation p(HBP:"VQIINK motif") View Subject | View Object

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) positiveCorrelation p(HBP:"VQIVYK motif") View Subject | View Object

We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs. PubMed:11606569

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

For this purpose, we focused on the well-characterized DK280 mutation (10–13), which specifically leads to aggregation-mediated toxicity. PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Overall, Tau, both in the soluble and in the insoluble fractions, was phosphorylated to a higher degree in the pro-aggregant strain compared with the other two strains. PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:locomotion) View Subject | View Object

The motility of the pro-aggregant worms was considerably enhanced upon apply- ing RNAi against F3DK280 (speed ¼ 70.7 + 17 mm/s for RNAi-treated versus 40.3 + 17 for control), whereas the anti- aggregant worms showed no difference upon treatment (Sup- plementary Material, Fig. S1C). PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:"dorsal spinal cord development") View Subject | View Object

In contrast, we observed severe developmental defects in the pro-aggregant strain (BR5707) that manifest as increased numbers of persist- ent gaps in both the ventral and dorsal neural cords (mean + SD ¼ 2.7 + 1.4 gaps at the L3 stage). PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:"dorsal spinal cord development") View Subject | View Object

In contrast, the pro-aggregant strain showed frequent occurrence of gaps (27.8 + 4.8% of day 1 adult animals), similar to those observed in the GABAergic neurons (Fig. 3E and Supplementary Material, Fig. S3). PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:"ventral spinal cord development") View Subject | View Object

In contrast, we observed severe developmental defects in the pro-aggregant strain (BR5707) that manifest as increased numbers of persist- ent gaps in both the ventral and dorsal neural cords (mean + SD ¼ 2.7 + 1.4 gaps at the L3 stage). PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:"ventral spinal cord development") View Subject | View Object

In contrast, the pro-aggregant strain showed frequent occurrence of gaps (27.8 + 4.8% of day 1 adult animals), similar to those observed in the GABAergic neurons (Fig. 3E and Supplementary Material, Fig. S3). PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) increases path(HBP:neurotoxicity) View Subject | View Object

From these data, we conclude that the continued expression of FL Tau V337M and F3DK280 is toxic for the neurons and as a conse- quence, the development of the nervous system is perturbed. PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:"nervous system development") View Subject | View Object

From these data, we conclude that the continued expression of FL Tau V337M and F3DK280 is toxic for the neurons and as a conse- quence, the development of the nervous system is perturbed. PubMed:22611162

p(HGNC:MAPT, var("p.Lys280del")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Tau protein with mutations in or near the microtubule-binding domain (for instance, G272V, N279K, ΔK280, P301L, V337M or R406W) tend to have a reduced affinity for microtubules and an increased tendency for aggregation PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

Tau protein with mutations in or near the microtubule-binding domain (for instance, G272V, N279K, ΔK280, P301L, V337M or R406W) tend to have a reduced affinity for microtubules and an increased tendency for aggregation PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

Disruption of these motifs (for example, by Pro mutations) abrogates the tendency for tau to aggregate; by contrast, strengthening the β‑structure with certain mutations (for instance, ΔK280 or P301L) accelerates tau aggregation both in vitro and in vivo PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

In a cellular model of tauopathy, cells expressing the ΔK280 repeat-domain-mutant tau show tau aggregation that depends on the stepwise proteolysis of the N‑terminal domain by a thrombin-like protease and of the C‑terminal domain by cathepsin L, generating a fragment (F3) that leads to robust aggregation in cell and animal models PubMed:26631930

Annotations
MeSH
Tauopathies

p(HGNC:MAPT, var("p.Lys280del")) decreases p(HBP:"4R tau") View Subject | View Object

However, there are also other mutations (such as ΔK280, L266V and G272V) that inhibit the inclusion of E10 and thus reduce the 4R-to-3R ratio PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases p(HBP:"3R tau") View Subject | View Object

However, there are also other mutations (such as ΔK280, L266V and G272V) that inhibit the inclusion of E10 and thus reduce the 4R-to-3R ratio PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases bp(GO:memory) View Subject | View Object

Remarkably, in two regulatable transgenic mouse models expressing human tau with the P301L mutation (rTg4510) or expressing the repeat domain of tau with the ΔK280 mutation, switching off tau expression improved memory impairment even though NFTs remained, clearly showing that tau aggregates are not sufficient for neurodegeneration and the cognitive effects that are typically observed in these models PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"somatodendritic compartment")) View Subject | View Object

The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) increases a(GO:"neurofibrillary tangle") View Subject | View Object

The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:cognition) View Subject | View Object

The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.