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Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy

Alpha-synuclein (aSyn) is implicated in Parkinson’s disease and several other neurodegenerative disorders. To date, the function and intracellular dynamics of aSyn are still unclear. Here, we tracked the dynamics of aSyn using photoactivatable green fluorescent protein as a reporter. We found that t...

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Detalles Bibliográficos
Autores principales: Gonçalves, Susana, Outeiro, Tiago Fleming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Humana Press Inc 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637893/
https://www.ncbi.nlm.nih.gov/pubmed/23389286
http://dx.doi.org/10.1007/s12035-013-8406-x
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author Gonçalves, Susana
Outeiro, Tiago Fleming
author_facet Gonçalves, Susana
Outeiro, Tiago Fleming
author_sort Gonçalves, Susana
collection PubMed
description Alpha-synuclein (aSyn) is implicated in Parkinson’s disease and several other neurodegenerative disorders. To date, the function and intracellular dynamics of aSyn are still unclear. Here, we tracked the dynamics of aSyn using photoactivatable green fluorescent protein as a reporter. We found that the availability of the aSyn N terminus modulates its shuttling into the nucleus. Interestingly, familial aSyn mutations altered the dynamics at which the protein distributes throughout the cell. Both the A30P and A53T aSyn mutations increase the speed at which the protein moves between the nucleus and cytoplasm, respectively. We also found that specific kinases potentiate the shuttling of aSyn between nucleus and cytoplasm. A mutant aSyn form that blocks S129 phosphorylation, S129A, results in the formation of cytoplasmic inclusions, suggesting phosphorylation modulates aggregation in addition to modulating aSyn intracellular dynamics. Finally, we found that the molecular chaperone HSP70 accelerates the entry of aSyn into the nuclear compartment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-013-8406-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-36378932013-04-29 Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy Gonçalves, Susana Outeiro, Tiago Fleming Mol Neurobiol Article Alpha-synuclein (aSyn) is implicated in Parkinson’s disease and several other neurodegenerative disorders. To date, the function and intracellular dynamics of aSyn are still unclear. Here, we tracked the dynamics of aSyn using photoactivatable green fluorescent protein as a reporter. We found that the availability of the aSyn N terminus modulates its shuttling into the nucleus. Interestingly, familial aSyn mutations altered the dynamics at which the protein distributes throughout the cell. Both the A30P and A53T aSyn mutations increase the speed at which the protein moves between the nucleus and cytoplasm, respectively. We also found that specific kinases potentiate the shuttling of aSyn between nucleus and cytoplasm. A mutant aSyn form that blocks S129 phosphorylation, S129A, results in the formation of cytoplasmic inclusions, suggesting phosphorylation modulates aggregation in addition to modulating aSyn intracellular dynamics. Finally, we found that the molecular chaperone HSP70 accelerates the entry of aSyn into the nuclear compartment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-013-8406-x) contains supplementary material, which is available to authorized users. Humana Press Inc 2013-02-08 2013 /pmc/articles/PMC3637893/ /pubmed/23389286 http://dx.doi.org/10.1007/s12035-013-8406-x Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Gonçalves, Susana
Outeiro, Tiago Fleming
Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title_full Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title_fullStr Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title_full_unstemmed Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title_short Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy
title_sort assessing the subcellular dynamics of alpha-synuclein using photoactivation microscopy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637893/
https://www.ncbi.nlm.nih.gov/pubmed/23389286
http://dx.doi.org/10.1007/s12035-013-8406-x
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