Sökning: WFRF:(Rüdiger S) >
Regulation of alpha...
Regulation of alpha-synuclein by chaperones in mammalian cells
-
- Burmann, Björn Marcus, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Wallenberg Centre for Molecular and Translational Medicine,Department of Chemistry and Molecular Biology
-
Gerez, J. A. (författare)
-
- Matečko-Burmann, Irena (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine
-
visa fler...
-
Campioni, S. (författare)
-
Kumari, P. (författare)
-
Ghosh, D. (författare)
-
Mazur, A. (författare)
-
- Aspholm, Emelie E. (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Wallenberg Centre for Molecular and Translational Medicine,Department of Chemistry and Molecular Biology
-
- Šulskis, Darios (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
-
Wawrzyniuk, M. (författare)
-
Bock, T. (författare)
-
Schmidt, A. (författare)
-
Rudiger, S. G. D. (författare)
-
Riek, R. (författare)
-
Hiller, S. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2019-12-04
- 2020
- Engelska.
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7788, s. 127-32
- Relaterad länk:
-
https://gupea.ub.gu....
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Neurodegeneration in patients with Parkinson's disease is correlated with the occurrence of Lewy bodies-intracellular inclusions that contain aggregates of the intrinsically disordered protein alpha-synuclein(1). The aggregation propensity of alpha-synuclein in cells is modulated by specific factors that include post-translational modifications(2,3), Abelson-kinase-mediated phosphorylation(4,5) and interactions with intracellular machineries such as molecular chaperones, although the underlying mechanisms are unclear(6-8). Here we systematically characterize the interaction of molecular chaperones with alpha-synuclein in vitro as well as in cells at the atomic level. We find that six highly divergent molecular chaperones commonly recognize a canonical motif in alpha-synuclein, consisting of the N terminus and a segment around Tyr39, and hinder the aggregation of alpha-synuclein. NMR experiments(9) in cells show that the same transient interaction pattern is preserved inside living mammalian cells. Specific inhibition of the interactions between alpha-synuclein and the chaperone HSC70 and members of the HSP90 family, including HSP90 beta, results in transient membrane binding and triggers a remarkable re-localization of alpha-synuclein to the mitochondria and concomitant formation of aggregates. Phosphorylation of alpha-synuclein at Tyr39 directly impairs the interaction of alpha-synuclein with chaperones, thus providing a functional explanation for the role of Abelson kinase in Parkinson's disease. Our results establish a master regulatory mechanism of alpha-synuclein function and aggregation in mammalian cells, extending the functional repertoire of molecular chaperones and highlighting new perspectives for therapeutic interventions for Parkinson's disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- c-abl
- complex
- conformation
- specificity
- reveals
- binding
- forms
- skp
- Science & Technology - Other Topics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
Nature
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
-
Burmann, Björn M ...
-
Gerez, J. A.
-
Matečko-Burmann, ...
-
Campioni, S.
-
Kumari, P.
-
Ghosh, D.
-
visa fler...
-
Mazur, A.
-
Aspholm, Emelie ...
-
Šulskis, Darios
-
Wawrzyniuk, M.
-
Bock, T.
-
Schmidt, A.
-
Rudiger, S. G. D ...
-
Riek, R.
-
Hiller, S.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
- Artiklar i publikationen
-
Nature
- Av lärosätet
-
Göteborgs universitet