Cargando…

Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration

The exact mechanisms leading to neurodegeneration in Alzheimer's disease (AD) and other tauopathies are not yet entirely understood. However, it is known that several RNA‐binding proteins (RBPs) form toxic aggregates and also interact with tau in such granules in tauopathies, including AD. The...

Descripción completa

Detalles Bibliográficos
Autores principales: Montalbano, Mauro, McAllen, Salome, Sengupta, Urmi, Puangmalai, Nicha, Bhatt, Nemil, Ellsworth, Anna, Kayed, Rakez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826126/
https://www.ncbi.nlm.nih.gov/pubmed/31532069
http://dx.doi.org/10.1111/acel.13035
_version_ 1783465019276525568
author Montalbano, Mauro
McAllen, Salome
Sengupta, Urmi
Puangmalai, Nicha
Bhatt, Nemil
Ellsworth, Anna
Kayed, Rakez
author_facet Montalbano, Mauro
McAllen, Salome
Sengupta, Urmi
Puangmalai, Nicha
Bhatt, Nemil
Ellsworth, Anna
Kayed, Rakez
author_sort Montalbano, Mauro
collection PubMed
description The exact mechanisms leading to neurodegeneration in Alzheimer's disease (AD) and other tauopathies are not yet entirely understood. However, it is known that several RNA‐binding proteins (RBPs) form toxic aggregates and also interact with tau in such granules in tauopathies, including AD. The Musashi (MSI) family of RBPs, consisting of two homologues: Musashi1 and Musashi2, have not been extensively investigated in neurodegenerative diseases. Here, using a tau inducible HEK (iHEK) model we investigate whether MSI proteins contribute to the aggregation of toxic tau oligomers (TauO). Wild‐type and mutant P301L tau iHEK cells are used to study the effect of different tau variants on the cellular localization of MSI proteins. Interestingly, we observe that tau co‐localizes with MSI in the cytoplasm and nuclei, altering the nuclear transport of MSI. Furthermore, incremental changes in the size and density of nuclear MSI/tau foci are observed. We also report here that TauO interact with MSI to cause the formation of distinct nuclear aggregates. Moreover, tau/MSI aggregates induce structural changes to LaminB1, leading to nuclear instability. These results illustrate a possible mechanism of neurodegeneration mediated by the aggregation of MSI proteins and TauO, suggesting that MSI plays a critical role in cellular dysfunction.
format Online
Article
Text
id pubmed-6826126
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-68261262019-12-01 Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration Montalbano, Mauro McAllen, Salome Sengupta, Urmi Puangmalai, Nicha Bhatt, Nemil Ellsworth, Anna Kayed, Rakez Aging Cell Original Articles The exact mechanisms leading to neurodegeneration in Alzheimer's disease (AD) and other tauopathies are not yet entirely understood. However, it is known that several RNA‐binding proteins (RBPs) form toxic aggregates and also interact with tau in such granules in tauopathies, including AD. The Musashi (MSI) family of RBPs, consisting of two homologues: Musashi1 and Musashi2, have not been extensively investigated in neurodegenerative diseases. Here, using a tau inducible HEK (iHEK) model we investigate whether MSI proteins contribute to the aggregation of toxic tau oligomers (TauO). Wild‐type and mutant P301L tau iHEK cells are used to study the effect of different tau variants on the cellular localization of MSI proteins. Interestingly, we observe that tau co‐localizes with MSI in the cytoplasm and nuclei, altering the nuclear transport of MSI. Furthermore, incremental changes in the size and density of nuclear MSI/tau foci are observed. We also report here that TauO interact with MSI to cause the formation of distinct nuclear aggregates. Moreover, tau/MSI aggregates induce structural changes to LaminB1, leading to nuclear instability. These results illustrate a possible mechanism of neurodegeneration mediated by the aggregation of MSI proteins and TauO, suggesting that MSI plays a critical role in cellular dysfunction. John Wiley and Sons Inc. 2019-09-18 2019-12 /pmc/articles/PMC6826126/ /pubmed/31532069 http://dx.doi.org/10.1111/acel.13035 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Montalbano, Mauro
McAllen, Salome
Sengupta, Urmi
Puangmalai, Nicha
Bhatt, Nemil
Ellsworth, Anna
Kayed, Rakez
Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title_full Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title_fullStr Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title_full_unstemmed Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title_short Tau oligomers mediate aggregation of RNA‐binding proteins Musashi1 and Musashi2 inducing Lamin alteration
title_sort tau oligomers mediate aggregation of rna‐binding proteins musashi1 and musashi2 inducing lamin alteration
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826126/
https://www.ncbi.nlm.nih.gov/pubmed/31532069
http://dx.doi.org/10.1111/acel.13035
work_keys_str_mv AT montalbanomauro tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT mcallensalome tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT senguptaurmi tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT puangmalainicha tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT bhattnemil tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT ellsworthanna tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration
AT kayedrakez tauoligomersmediateaggregationofrnabindingproteinsmusashi1andmusashi2inducinglaminalteration