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PMID:19363271

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Citation

Tortosa, E, Santa-Maria, I, Moreno, F, Lim, F, Perez, M and Avila, J (2009) Binding of Hsp90 to tau promotes a conformational change and aggregation of tau protein. J. Alzheimers Dis. 17:319-25

Abstract

Tau pathology, associated with Alzheimer's disease, is characterized by the presence of phosphorylated and aggregated tau. Phosphorylation of tau takes place mainly in the vicinity of the tubulin-binding region of the molecule and its self aggregation is also mediated via this tubulin-binding region. Tau phosphorylation and aggregation have been related with conformational changes of the protein. These changes could be regulated by chaperones such as heat shock proteins, since one of these, heat shock protein 90 (Hsp90), has already been described as a putative tau-binding protein. In this work, we have confirmed the interaction of Hsp90 with tau protein and report that binding of Hsp90 to tau facilitates a conformational change that could result in its phosphorylation by glycogen synthase kinase 3 and its aggregation into filamentous structures.

Links

PubMed Online version:10.3233/JAD-2009-1049

Keywords

Animals; Biophysical Phenomena/physiology; Brain/metabolism; Glycogen Synthase Kinase 3/metabolism; Glycogen Synthase Kinase 3 beta; HSP90 Heat-Shock Proteins/metabolism; HSP90 Heat-Shock Proteins/ultrastructure; Humans; Immunoblotting/methods; Immunoprecipitation/methods; Microscopy, Electron, Scanning/methods; Phosphorylation; Protein Binding/drug effects; Protein Binding/physiology; Protein Conformation; Rats; tau Proteins/metabolism; tau Proteins/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HS90A

involved_in

GO:0032273: positive regulation of protein polymerization

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P10636)

Seeded From UniProt

complete

HUMAN:HS90A

enables

GO:0048156: tau protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19332

F

  • occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P10636)

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:1902949: positive regulation of tau-protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P49841)

Seeded From UniProt

complete

RAT:TAU

enables

GO:0051879: Hsp90 protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07900

F

  • occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

RAT:HS90A

enables

GO:0048156: tau protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:69329

F

Seeded From UniProt

complete

RAT:TAU

enables

GO:0051879: Hsp90 protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07900

F

occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

RAT:TAU

enables

GO:0051879: Hsp90 protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:631409

F

Seeded From UniProt

complete

HUMAN:HS90A

enables

GO:0048156: tau protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19332

F

occurs_in:(UBERON:0000955)

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:1902949: positive regulation of tau-protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P49841)

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P10636)

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:0032273: positive regulation of protein polymerization

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:P10636)

Seeded From UniProt

complete

Notes

See also

References

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