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complex(a(GO:microtubule), p(HGNC:MAPT))

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Components

Appears in Networks 6

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

Caenorhabditis elegans models of tauopathy v1.0.0

Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated degenerative changes v1.0.0

Tau in physiology and pathology v1.0.0

In-Edges 31

p(HGNC:MAPT) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In general, phosphorylation of tau reduces its affinity for microtubules [30], while dephosphorylation via enzymes such as PP2A and PP5 restores binding PubMed:21882945

Appears in Networks:

p(FPLX:HSP90) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Hsp90 was also shown to increase association of tau with microtubules [114]; however, its binding is not well characterized and it is not known whether this is a direct or indirect process PubMed:21882945

Appears in Networks:

complex(a(MESH:"Protein Phosphatase 2"), p(HGNC:MAPT)) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Finally, the FKBP51–Hsp90 complex has been proposed to be responsible for the interaction of tau with phosphatases, helping to restore binding to microtubules [137]. PubMed:21882945

Appears in Networks:

p(INTERPRO:"Heat shock protein 70 family") increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Hsp70 has been shown to both stabilize binding of tau to microtubules [114] and promote its degradation in combination with CHIP [115,116] PubMed:21882945

Appears in Networks:

p(HGNC:FKBP5) regulates complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Recently, the co-chaperone FK506-binding protein 51 kDa (FKBP51) has been implicated as a modulator of tau binding to microtubules PubMed:21882945

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) regulates complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Phosphorylation of tau by the kinases GSK3b, Cdk5 and MARK2 is a major regulator of its microtubule interactions PubMed:21882945

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In general, phosphorylation of tau reduces its affinity for microtubules [30], while dephosphorylation via enzymes such as PP2A and PP5 restores binding PubMed:21882945

Appears in Networks:

p(HGNC:HSPA8) regulates complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In addition, recent work has demonstrated that Hsc70, the constitutive cytosolic form of Hsp70s, also dynamically regulates the association of tau with microtubules PubMed:21882945

Appears in Networks:

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

However, under potentially proteotoxic conditions, the post-translational modifications or mutations that damage tau’s affinity for microtubules and favor its aggregation are thought to generate a molecular ‘danger signal’ that specifically alerts the quality control system [112,113]. PubMed:21882945

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Specific inhibition of PP2A/Bα is associated with enhanced tau phosphorylation at many AD-like phospho epitopes, and subsequent inability of tau to bind to and stabilize microtubules (Sontag et al., 1996). PubMed:24653673

Appears in Networks:

complex(p(HGNC:PPP2CB), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Specific inhibition of PP2A/Bα is associated with enhanced tau phosphorylation at many AD-like phospho epitopes, and subsequent inability of tau to bind to and stabilize microtubules (Sontag et al., 1996). PubMed:24653673

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

However, when tau becomes hyperphosphorylated, it detaches from microtubules and aggregates, resulting in depolymerization of microtubules and formation of insoluble tau deposits [40] PubMed:29758300

Appears in Networks:

p(HGNC:MAPT) increases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Genetic interaction studies involving ptl-1 and mutants in other genes associated with microtubules such as mec-12 (a-tubulin) and mec-7 (btubulin), suggested a larger functional role of PTL-1 in mechanosensation (45). PubMed:29191965

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HBP:"Tau aggregates") negativeCorrelation complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

This suggests that the stabilization of the microtubule-bound conformation of tau may delay tau aggregation PubMed:26631930

Appears in Networks:

p(HGNC:MAPT) directlyIncreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In adult neurons, tau mainly distributes into axons, where it interacts with microtubules through the repeat-domain and flanking regions. PubMed:26631930

Appears in Networks:
Annotations
MeSH
Axons

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Hyperphosphorylation of tau at the repeat domain reduces its microtubule binding, which may cause microtubule disassembly, leading to axonal transport deficits. PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 18)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

The nitration of these Tyr residues alters the conformation of tau, reduces its binding to microtubules and, depending on the nitration sites, can promote or inhibit aggregation PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:glycation)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In addition, glycation of tau may reduce the binding of tau to microtubules PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 29)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

The nitration of these Tyr residues alters the conformation of tau, reduces its binding to microtubules and, depending on the nitration sites, can promote or inhibit aggregation PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 394)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

The nitration of these Tyr residues alters the conformation of tau, reduces its binding to microtubules and, depending on the nitration sites, can promote or inhibit aggregation PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Thus, it is possible that unknown cofactors trigger tau aggregation in the AD brain, whereas phosphorylation may accelerate aggregation indirectly: for example, by detaching tau from microtubules PubMed:26631930

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Ser, 214), pmod(Ph, Thr, 231)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In addition, phosphorylation of Ser214 and Thr231 in the flanking region of tau can trigger the detachment of tau from microtubules, whereas phosphorylation at other Thr-Pro or Ser-Pro motifs in the flanking region has only a weak influence on tau–microtubule binding PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 262)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Arg406Trp")) 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

Appears in Networks:

p(HGNC:MAPT, var("p.Asn279Lys")) 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

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) 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

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) 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

Appears in Networks:

p(HGNC:MAPT, var("p.Val337Met")) 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

Appears in Networks:

Out-Edges 7

complex(a(GO:microtubule), p(HGNC:MAPT)) hasComponent a(GO:microtubule) View Subject | View Object

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) hasComponent p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) decreases p(HGNC:MAPT, pmod(HBP:misfolded)) View Subject | View Object

In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(a(GO:microtubule), p(HGNC:MAPT)) increases bp(GO:"microtubule bundle formation") View Subject | View Object

Tau thereby stabilizes microtubules, promotes microtubule assembly and, in particular, regulates the dynamic instability of microtubules that allows reorganization of the cytoskeleton. PubMed:26631930

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) increases bp(GO:"actin cytoskeleton reorganization") View Subject | View Object

Tau thereby stabilizes microtubules, promotes microtubule assembly and, in particular, regulates the dynamic instability of microtubules that allows reorganization of the cytoskeleton. PubMed:26631930

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) negativeCorrelation a(HBP:"Tau aggregates") View Subject | View Object

This suggests that the stabilization of the microtubule-bound conformation of tau may delay tau aggregation PubMed:26631930

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Thus, it is possible that unknown cofactors trigger tau aggregation in the AD brain, whereas phosphorylation may accelerate aggregation indirectly: for example, by detaching tau from microtubules PubMed:26631930

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

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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.