Vimentin protects differentiating stem cells from stress

by Sundararaghavan Pattabiraman
Doctoral thesis
Date of Examination:2019-12-12
Date of issue:2020-12-10
Advisor:Prof. Dr. Daniel Kaganovich
Referee:Prof. Dr. Martin Göpfert
Referee:Prof. Dr. Tiago Fleming Outeiro
Persistent Address: http://dx.doi.org/10.53846/goediss-8320

 

 

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Abstract

English

Vimentin is the first cytoplasmic intermediate filament to be expressed in mammalian cells during early differentiation, but its role in cellular fitness has long been a mystery. Vimentin is acknowledged to play a role in cell stiffness, cell motility, and cytoplasmic organization, yet it is thought to be dispensable for cellular function and organismal development. Here, we show that Vimentin plays a role in cellular stress response in differentiating cells, by directly binding aggregates and RNA-binding proteins, directing their elimination and asymmetric partitioning. In the absence of Vimentin, pluripotent embryonic stem cells fail to differentiate properly, with a pronounced deficiency in neuronal differentiation. Our results uncover a novel function for Vimentin, with important implications for development, tissue homeostasis, and in particular, stress response.
Keywords: Vimentin, Intermediate Filaments, Aggregation, Stress Granules, RNP Granules, Asymmetric Inheritance, Aging, Differentiation, Embryonic Stem Cells
 
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