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Jinwal UK, O'Leary JC, Borysov SI, Jones JR, Li Q, Koren J, Abisambra JF, Vestal GD, Lawson LY, Johnson AG, Blair LJ, Jin Y, Miyata Y, Gestwicki JE, Dickey CA.
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The microtubule-associated protein Tau plays a crucial role in regulating the dynamic stability of microtubules during neuronal development and synaptic transmission. In a group of neurodegenerative diseases, such as Alzheimer disease and other tauopathies, conformational changes in Tau are associated with the initial stages of disease pathology. Folding of Tau into the MC1 conformation, where the amino acids at residues 7-9 interact with residues 312-342, is one of the earliest pathological alterations of Tau in Alzheimer disease. The mechanism of this conformational change in Tau and the subsequent effect on function and association to microtubules is largely unknown. Recent work by our group and others suggests that members of the Hsp70 family play a significant role in Tau regulation. Our new findings suggest that heat shock cognate (Hsc) 70 facilitates Tau-mediated microtubule polymerization. The association of Hsc70 with Tau was rapidly enhanced following treatment with microtubule-destabilizing agents. The fate of Tau released from the microtubule was found to be dependent on ATPase activity of Hsc70. Microtubule destabilization also rapidly increased the MC1 folded conformation of Tau. An in vitro assay suggests that Hsc70 facilitates formation of MC1 Tau. However, in a hyperphosphorylating environment, the formation of MC1 was abrogated, but Hsc70 binding to Tau was enhanced. Thus, under normal circumstances, MC1 formation may be a protective conformation facilitated by Hsc70. However, in a diseased environment, Hsc70 may preserve Tau in a more unstructured state, perhaps facilitating its pathogenicity.
Abisambra,
LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease.
2010, Pubmed
Abisambra,
LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease.
2010,
Pubmed Barghorn,
Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain.
2004,
Pubmed Ben-Zvi,
Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones.
2001,
Pubmed Bolte,
A guided tour into subcellular colocalization analysis in light microscopy.
2006,
Pubmed Braak,
Neuropathological stageing of Alzheimer-related changes.
1991,
Pubmed Carmel,
The structural basis of monoclonal antibody Alz50's selectivity for Alzheimer's disease pathology.
1996,
Pubmed Carty,
Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice.
2008,
Pubmed Chen,
Translocation of constitutively expressed heat shock protein Hsc70 to synapse-enriched areas of the cerebral cortex after hyperthermic stress.
2007,
Pubmed Clavaguera,
Transmission and spreading of tauopathy in transgenic mouse brain.
2009,
Pubmed Desai,
Kin I kinesins are microtubule-destabilizing enzymes.
1999,
Pubmed
,
Xenbase Dickey,
Akt and CHIP coregulate tau degradation through coordinated interactions.
2008,
Pubmed Dickey,
Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy.
2009,
Pubmed Dickey,
The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins.
2007,
Pubmed Dou,
Chaperones increase association of tau protein with microtubules.
2003,
Pubmed D'Souza,
Constitutive expression of heat shock proteins Hsp90, Hsc70, Hsp70 and Hsp60 in neural and non-neural tissues of the rat during postnatal development.
1998,
Pubmed Goedert,
Tau gene mutation in familial progressive subcortical gliosis.
1999,
Pubmed Grundke-Iqbal,
Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology.
1986,
Pubmed Hardy,
The genetics of neurodegenerative diseases.
2006,
Pubmed Hartl,
Converging concepts of protein folding in vitro and in vivo.
2009,
Pubmed Hernández,
GSK3: a possible link between beta amyloid peptide and tau protein.
2010,
Pubmed Hutton,
Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.
1998,
Pubmed Jeganathan,
The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments.
2008,
Pubmed Jicha,
Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau.
1997,
Pubmed Jinwal,
The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules.
2010,
Pubmed
,
Xenbase Jinwal,
Chemical manipulation of hsp70 ATPase activity regulates tau stability.
2009,
Pubmed Khalilzadeh,
Epothilone-paclitaxel resistant leukemic cells CEM/dEpoB300 are sensitive to albendazole: Involvement of apoptotic pathways.
2007,
Pubmed King,
Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid.
2006,
Pubmed Koren,
Facilitating Akt clearance via manipulation of Hsp70 activity and levels.
2010,
Pubmed Liang,
Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome.
2008,
Pubmed Manzerra,
Tissue-specific differences in heat shock protein hsc70 and hsp70 in the control and hyperthermic rabbit.
1997,
Pubmed Mayer,
Hsp70 chaperones: cellular functions and molecular mechanism.
2005,
Pubmed Meriin,
Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1.
2002,
Pubmed Morano,
New tricks for an old dog: the evolving world of Hsp70.
2007,
Pubmed Pérez,
In vitro assembly of tau protein: mapping the regions involved in filament formation.
2001,
Pubmed Petrucelli,
CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation.
2004,
Pubmed Rasband,
Converging on the origins of axonal ion channel clustering.
2009,
Pubmed Ryu,
Assessment of substrate-stabilizing factors for DnaK on the folding of aggregation-prone proteins.
2008,
Pubmed Sarkar,
Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone.
2008,
Pubmed Sevcik,
Structure solution of misfolded conformations adopted by intrinsically disordered Alzheimer's tau protein.
2009,
Pubmed Spillantini,
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia.
1998,
Pubmed Spires-Jones,
In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons.
2008,
Pubmed Tohgi,
Heat-shock cognate 70 messenger RNA expression in postmortem human hippocampus: regional differences and age-related changes.
1995,
Pubmed Tortosa,
Binding of Hsp90 to tau promotes a conformational change and aggregation of tau protein.
2009,
Pubmed Uboga,
Formation of diffuse and fibrillar tangles in aging and early Alzheimer's disease.
2000,
Pubmed Weaver,
Conformational change as one of the earliest alterations of tau in Alzheimer's disease.
2000,
Pubmed Wolfe,
Tau mutations in neurodegenerative diseases.
2009,
Pubmed
