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Cellular senescence is associated with reorganization of the microtubule cytoskeleton

  • Ossama Moujaber
  • Francine Fishbein
  • Nawal Omran
  • Yue Liang
  • Inés Colmegna
  • John F. Presley
  • Ursula Stochaj
Original Article
  • 185 Downloads

Abstract

Senescent cells undergo structural and functional changes that affect essentially every aspect of cell physiology. To date, the impact of senescence on the cytoskeleton is poorly understood. This study evaluated the cytoskeleton in two independent cellular models of kidney epithelium senescence. Our work identified multiple senescence-related alterations that impact microtubules and filamentous actin during interphase. Both filamentous systems reorganized profoundly when cells became senescent. As such, microtubule stability increased during senescence, making these filaments more resistant to disassembly in the cold or by nocodazole. Microtubule stabilization was accompanied by enhanced α-tubulin acetylation on lysine 40 and the depletion of HDAC6, the major deacetylase for α-tubulin lysine 40. Rho-associated kinase Rock1 is an upstream regulator that modulates key properties of the cytoplasmic cytoskeleton. Our research shows that Rock1 concentrations were reduced significantly in senescent cells, and we revealed a mechanistic link between microtubule stabilization and Rock1 depletion. Thus, Rock1 overexpression partially restored the cold sensitivity of microtubules in cells undergoing senescence. Additional components relevant to microtubules were affected by senescence. Specifically, we uncovered the senescence-related loss of the microtubule nucleating protein γ-tubulin and aberrant formation of γ-tubulin foci. Concomitant with the alterations of microtubule and actin filaments, senescent cells displayed functional changes. In particular, cell migration was impaired significantly in senescent cells. Taken together, our study identified new senescence-associated deficiencies of the microtubule and actin cytoskeleton, provided insights into the underlying molecular mechanisms and demonstrated functional consequences that are important to the physiology and function of renal epithelial cells.

Keywords

Epithelial cell Senescence Cytoskeleton Microtubules F-actin Rock1 Cell migration 

Notes

Acknowledgements

This work was supported by Grants from NSERC (Natural Sciences and Engineering Research Council of Canada) to US and JFP. We thank Dr. M. Lora for performing the flow cytometry, and Drs. G. Brouhard (McGill University) and G. Gomez (University of Queensland, St. Lucia, Brisbane) for their generous gift of reagents.

Supplementary material

18_2018_2999_MOESM1_ESM.pdf (988 kb)
Supplementary material 1 (PDF 988 kb)

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PhysiologyMcGill UniversityMontrealCanada
  2. 2.Department of RheumatologyMcGill UniversityMontrealCanada
  3. 3.Department of Anatomy and Cell BiologyMcGill UniversityMontrealCanada

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