Cysteine Oxidation of Tau and Microtubule-associated Protein-2 by Peroxynitrite

Landino, Lisa M.; Skreslet, Tabor E.; Alston, Jane A.

doi:10.1074/jbc.m405471200

Cited by 81 publications

(29 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In similar conditions but in the absence of DTT, no titration could be observed. This result is in agreement with previous work, which showed that the affinity of Tau for microtubules decreases in the absence of DTT using co-sedimentation and NMR titration assays (37,38).…”

Section: Resultssupporting

confidence: 93%

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

Lefèvre¹,

Chernov

Joshi

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

The C-terminal region of tubulin is involved in multiple aspects of the regulation of microtubule assembly. To elucidate the molecular mechanisms of this regulation, we study here, using different approaches, the interaction of Tau Microtubules are involved in a number of critical cellular processes, such as the determination of cell shape, chromosome segregation, intracellular transport of vesicles and organelles, and cell migration. Microtubules consist mainly of ␣␤-tubulin heterodimers organized head-to-tail into protofilaments whose parallel self-association gives rise to microtubules (1-4). ␣-and ␤-tubulin monomers have each a molecular mass of 50 kDa and are organized in three domains, namely the N-terminal domain (amino acid residues 1-205) involved in nucleotide binding, the intermediate domain (amino acid residues 206 -384), and the C-terminal domain (amino acid residue 385 to the C terminus) (5). The C-terminal domain of tubulin represents a critical part of the binding site of different tubulin/microtubules partners, such as MAPs, 4 which are major regulators of microtubule dynamics (6 -8), or polycations, which promote tubulin assembly in vitro in different polymeric forms (9). The C-terminal domain comprises a highly negatively charged tail of about 20 amino acid residues (named herein the C-terminal tail (CTT)), which protrudes from the surface of microtubules. In agreement with its participation in the regulation of microtubule assembly through interactions with partners, the CTT is also the most divergent part of tubulin, and variations among tubulin isotypes (10) may explain the modulation of the dynamics of microtubule assembly in specific tissues or cytoplasmic regions.Different structure information has been obtained regarding the C-terminal domain of tubulin by using either fulllength tubulin or peptide fragments. Electron crystallography of zinc-induced tubulin sheets showed the presence of two anti-parallel ␣-helices (helix H11 (amino acid residues 385-397) and helix H12 (amino acid residues 418 -433)) lying at the outer surface of tubulin. The regions corresponding to the CTTs of either ␣-or ␤-tubulin were however not observed, probably due to the flexibility of this part of the protein (5). These observations were confirmed by x-ray diffraction analyses of crystal complexes formed between tubulin and the RB3-stathmin-like domain (11-13). Other structural data were obtained with peptides from the C-terminal region of tubulin studied either when free in solution or in interaction with different partners. NMR structure investigations on ␣-and ␤-tubulin C-terminal peptides showed that both ␣ (residues 404 -451) and ␤ (residues 394 -445) peptides have no defined secondary structure in aqueous solution but contain a well □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental 4 The abbreviations used are: MAP, microtubule-associated protein; ␣Tub410C, amino acid residues 410 -451 from ␣1a-tubulin; CTT, tubulin C-terminal tail; ITC, isothermal titration ...

show abstract

Section: Resultssupporting

confidence: 93%

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

Lefèvre¹,

Chernov

Joshi

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Another possible consequence of higher oxidative stress levels could be an acceleration of tau pathology (72,73). Moreover, tau can be readily oxidized by H 2 O 2 to form disulfide-linked species that manifest reduced propensity to promote microtubule assembly (74). Oxidized tau then becomes a substrate of the thioredoxin reductase and glutathione/glutaredoxin reductase systems (74,75).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, tau can be readily oxidized by H 2 O 2 to form disulfide-linked species that manifest reduced propensity to promote microtubule assembly (74). Oxidized tau then becomes a substrate of the thioredoxin reductase and glutathione/glutaredoxin reductase systems (74,75). Thereby, we can speculate that the accumulation of oxidized P301L tau might overload these antioxidant regenerating systems, causing further oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Functional Analyses Reveal a Mitochondrial Dysfunction in P301L Tau Transgenic Mice

David

Hauptmann

Scherping

et al. 2005

Journal of Biological Chemistry

388

311

View full text Add to dashboard Cite

Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated tau and develop neurofibrillary tangles. The consequences of tau pathology were investigated here by proteomics followed by functional analysis. Mainly metabolism-related proteins including mitochondrial respiratory chain complex components, antioxidant enzymes, and synaptic proteins were identified as modified in the proteome pattern of P301L tau mice. Significantly, the reduction in mitochondrial complex V levels in the P301L tau mice revealed using proteomics was also confirmed as decreased in human P301L FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) brains. Functional analysis demonstrated a mitochondrial dysfunction in P301L tau mice together with reduced NADH-ubiquinone oxidoreductase activity and, with age, impaired mitochondrial respiration and ATP synthesis. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species in aged transgenic mice. Increased tau pathology as in aged homozygous P301L tau mice revealed modified lipid peroxidation levels and the upregulation of antioxidant enzymes in response to oxidative stress. Furthermore, P301L tau mitochondria displayed increased vulnerability toward ␤-amyloid (A␤) peptide insult, suggesting a synergistic action of tau and A␤ pathology on the mitochondria. Taken together, we conclude that tau pathology involves a mitochondrial and oxidative stress disorder possibly distinct from that caused by A␤. Alzheimer disease (AD)1 is characterized by two major histopathological hallmarks, extracellular plaques of fibrillar ␤-amyloid (A␤) peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (1, 2). Mutations in tau have been identified in a related neurodegenerative disorder called frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with NFT formation in the absence of plaque formation (3-5). Transgenic mice overexpressing the P301L mutant human tau protein were created to model tauopathies in vivo (6, 7). These mice show an accumulation of hyperphosphorylated tau and NFT formation similar to those in FTDP-17 and AD.Little is known about the distinct intracellular mechanisms underlying the consequences of tau pathology. This insight could help us to understand the selective vulnerability of cells with tau pathology and thereby the pathogenesis of AD. Increasing evidence highlights a connection between AD and mitochondrial dysfunction together with a deregulation of energy metabolism and oxidative stress (8). Various reports have demonstrated markedly reduced levels of mitochondrial proteins and activities (9 -11), decreased glucose turnover (12, 13), increased mitochondrial DNA mutations (14 -16), and increased lipid peroxidation (17-19) in AD brains.To examine the contribution of tau to these neurodegenerative processes, we carried out a proteomic analysis of our P301L tau transgenic mice. To zoom in on proteins relevant to the p...

show abstract

“…In-vitro, cysteine oxidation of tau by PN results in formation of disulfide crosslinks, tau oligomerization, and decreased microtubule assembly (Landino et al , 2004). PN can also promote tau oligomerization through addition of tyrosyl radicals which results in formation of 3,3′-dityrosine irreversible crosslinks and stabilization of insoluble tau filament aggregates characteristic of late stage paired helical filaments (PHF) (Reynolds et al , 2005; Reynolds et al , 2006).…”

Section: The Role Of Tau In Cellular Dysfunctionmentioning

confidence: 99%

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

Kulbe

Hall

2017

Progress in Neurobiology

View full text Add to dashboard Cite

In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, football, football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression.

show abstract

Cysteine Oxidation of Tau and Microtubule-associated Protein-2 by Peroxynitrite

Cited by 81 publications

References 31 publications

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

The C Terminus of Tubulin, a Versatile Partner for Cationic Molecules

Proteomic and Functional Analyses Reveal a Mitochondrial Dysfunction in P301L Tau Transgenic Mice

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

Contact Info

Product

Resources

About