ArticleThe Journal of biological chemistry2009
Transglutaminase-mediated intramolecular cross-linking of membrane-bound alpha-synuclein promotes amyloid formation in Lewy bodies.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis.Aging and disease · 2024Review
- Cross-Linked α-Synuclein as Inhibitor of Amyloid Formation.International journal of molecular sciences · 2023Article
- Dichlorvos-induced formation of isopeptide crosslinks between proteins in SH-SY5Y cells.Analytical biochemistry · 2022Article
- Naturally Occurring Epsilon Gamma Glutamyl Lysine Isopeptide Crosslinks in Human Neuroblastoma SH-SY5Y Cells.ACS omega · 2022Article
- Mass Spectrometric Identification of a Novel Factor XIIIa Cross-Linking Site in Fibrinogen.Proteomes · 2021Article
- Evaluation of mass spectrometry MS/MS spectra for the presence of isopeptide crosslinked peptides.PloS one · 2021Article
- Composition of the Intranuclear Inclusions of Fragile X-associated Tremor/Ataxia Syndrome.Acta neuropathologica communications · 2019Article
- Inflammation, Autoimmunity, and Hypertension: The Essential Role of Tissue Transglutaminase.American journal of hypertension · 2017Review
- Vertebrate food products as a potential source of prion-like α-synuclein.NPJ Parkinson's disease · 2017Review
- Transglutaminase 2 exacerbates α-synuclein toxicity in mice and yeast.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Tissue transglutaminase contributes to the pathogenesis of preeclampsia and stabilizes placental angiotensin receptor type 1 by ubiquitination-preventing isopeptide modification.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Transglutaminase is a therapeutic target for oxidative stress, excitotoxicity and stroke: a new epigenetic kid on the CNS block.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Review
- γ-Glutamylamines and neurodegenerative diseases.Amino acids · 2013Review
- Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Cellular functions of tissue transglutaminase.International review of cell and molecular biology · 2012Review
- Tissue transglutaminase-mediated glutamine deamidation of beta-amyloid peptide increases peptide solubility, whereas enzymatic cross-linking and peptide fragmentation may serve as molecular triggers for rapid peptide aggregation.The Journal of biological chemistry · 2011Article
- Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrin alpha9beta1.The Journal of biological chemistry · 2011Article
- Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson's disease brain.Brain pathology (Zurich, Switzerland) · 2011Article
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Authors and funding
6 authors.
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Abstract
The alpha-synuclein immunopositive and chaotrope-insoluble material from human brains with Lewy body pathology was analyzed by mass spectrometry. From the proteinase K-cleavable peripheral fraction of Lewy bodies, which was densely cross-linked by gamma-glutamyl-epsilon-lysine bonds between HspB1 and ubiquitin in a pattern similar to neurofibrillary tangles (Nemes, Z., Devreese, B., Steinert, P. M., Van Beeumen, J., and Fésüs, L. (2004) FASEB J. 18, 1135-1137), 53 proteins were identified. In the core of Lewy bodies only alpha-synuclein was found, and it contained a low amount of intramolecular cross-links between Gln-99 and Lys-58. In vitro cross-linking of alpha-synuclein by transglutaminases 1-3 and 5 produced a heterogeneous population of variably cross-linked alpha-synucleins in solution, which inhibited the aggregation of the protein into amyloid. However, in the presence of phosphatidylserine-rich membranes and micromolar calcium concentrations, the cross-linking by transglutaminases 1, 2, and 5 showed specificity toward the utilization of Gln-99 and Lys-58. As shown by thioflavin T fluorescence monitoring, the formation of this cross-link accelerated the aggregation of native alpha-synuclein. Chemical cross-linking of residues 58-99 triggered amyloid formation, whereas such bonding of residues 99 to 10 was inhibitory. Our findings reveal the pivotal role of membrane attachment and transglutaminase-mediated intermolecular cross-linking for the propagative misfolding and aggregation of alpha-synuclein.
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