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

Mauro Montalbano, Salome McAllen, Urmi Sengupta, Nicha Puangmalai, Nemil Bhatt, Anna Ellsworth, Rakez Kayed

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere13035
JournalAging Cell
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2019

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Tauopathies
Lamins
RNA-Binding Proteins
Poisons
Alzheimer Disease
tau Proteins
Cell Nucleus Active Transport
Neurodegenerative Diseases
Cytoplasm
Proteins

Keywords

  • Musashi
  • neurodegeneration
  • nuclear dysfunction
  • protein aggregation
  • tau

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

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.

In: Aging Cell, Vol. 18, No. 6, e13035, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Bhatt, Nemil

AU - Ellsworth, Anna

AU - Kayed, Rakez

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