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Sample Annotated Edges 5

a(GO:lysosome) increases deg(a(HBP:HBP00053)) View Subject | View Object

In agreement with our previous observations (Wang et al., 2009), we found that lysosomes contribute to degradation of WT tau (reflected as an increase in tau levels upon blockage of lysosomal proteolysis with inhibitors) PubMed:29024336

p(MGI:Mapt, var("p.Ala152Thr")) decreases deg(p(MGI:Mapt)) View Subject | View Object

Taken together, our in vitro and cell-based studies argue that these two point mutations, A152T and P301L, reduce the normal degradation of tau by CMA, although the P301L mutation has a more pronounced inhibitory effect PubMed:29024336

bp(GO:"chaperone-mediated autophagy") increases deg(p(MGI:Mapt, var("p.Ala152Thr"))) View Subject | View Object

In the case of tau-A152T, the dynamics of internalization/degradation through CMA were comparable to WT tau (Fig. 1c,d), in agreement with our studies in intact cells in culture (Fig. 1a, b), but we found a significantly higher amount of tau-A152T bound to the membrane of CMA-active lysosomes (Fig. 1c,d) PubMed:29024336

path(MESH:"Proteostasis Deficiencies") decreases deg(p(MGI:Mapt, var("p.Pro301Leu"))) View Subject | View Object

Interestingly, although tau-P301L was not degraded in lysosomes, blockage of CMA promoted accumulation of this protein variant, albeit at significantly lower levels than WT and A152T. We propose that overall loss of proteostasis as a consequence of CMA blockage could indirectly affect clearance of tau-P301L through other systems PubMed:29024336

complex(a(GO:lysosome), p(MGI:Mapt, var("p.Pro301Leu"))) increases tloc(p(MGI:Mapt, var("p.Pro301Leu")), fromLoc(MESH:"Extracellular Space"), toLoc(GO:lysosome)) View Subject | View Object

Reduced tau-P301L uptake is not caused by a problem in translocation across the lysosomal membrane, but rather by reduced targeting/binding to lysosomes, as we did not detect tau accumulation at the lysosomal membrane PubMed:29024336


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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.