Nestin as a regulator of Cdk5 in differentiating myoblasts

Hanna-Mari Pallari, Julia Lindqvist, Elin Torvaldson, Saima E. Ferraris, Tao He, Cecilia Sahlgren, John E. Eriksson

Research output: Contribution to journalArticleScientificpeer-review

30 Citations (Scopus)

Abstract

Many types of progenitor cells are distinguished by the expression of the intermediate filament protein nestin, a frequently used stem cell marker, the physiological roles of which are still unknown. Whereas myogenesis is characterized by dynamically regulated nestin levels, we studied how altering nestin levels affects myoblast differentiation. Nestin determined both the onset and pace of differentiation. Whereas depletion of nestin by RNAi strikingly accelerated the process, overexpression of nestin completely inhibited differentiation. Nestin down-regulation augmented the early stages of differentiation, at the level of cell-cycle withdrawal and expression of myogenic markers, but did not affect proliferation of undifferentiated dividing myoblasts. Nestin regulated the cleavage of the Cdk5 activator protein p35 to its degradation-resistant form, p25. In this way, nestin has the capacity to halt myoblast differentiation by inhibiting sustained activation of Cdk5 by p25, which is critical for the progress of differentiation. Our results imply that nestin regulates the early stages of myogenesis rather than maintains the undifferentiated state of progenitor cells. In the bidirectional interrelationship between nestin and Cdk5, Cdk5 regulates the organization and stability of its own nestin scaffold, which in turn controls the effects of Cdk5. This nestin–Cdk5 cross-talk sets the pace of muscle differentiation.
Original languageEnglish
Pages (from-to)1539-1549
JournalMolecular Biology of the Cell
Volume22
Issue number9
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

Nestin
Myoblasts
Stem Cells
Muscle Development
Cyclin-Dependent Kinase 5
Intermediate Filament Proteins
RNA Interference
Cell Cycle
Down-Regulation

Keywords

  • intermediate filaments
  • nestin
  • Cdk5 signaling
  • p35
  • muscle differentiation

Cite this

Pallari, H-M., Lindqvist, J., Torvaldson, E., Ferraris, S. E., He, T., Sahlgren, C., & Eriksson, J. E. (2011). Nestin as a regulator of Cdk5 in differentiating myoblasts. Molecular Biology of the Cell, 22(9), 1539-1549. https://doi.org/10.1091/mbc.E10-07-0568
Pallari, Hanna-Mari ; Lindqvist, Julia ; Torvaldson, Elin ; Ferraris, Saima E. ; He, Tao ; Sahlgren, Cecilia ; Eriksson, John E. / Nestin as a regulator of Cdk5 in differentiating myoblasts. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 9. pp. 1539-1549.
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Pallari, H-M, Lindqvist, J, Torvaldson, E, Ferraris, SE, He, T, Sahlgren, C & Eriksson, JE 2011, 'Nestin as a regulator of Cdk5 in differentiating myoblasts', Molecular Biology of the Cell, vol. 22, no. 9, pp. 1539-1549. https://doi.org/10.1091/mbc.E10-07-0568

Nestin as a regulator of Cdk5 in differentiating myoblasts. / Pallari, Hanna-Mari; Lindqvist, Julia; Torvaldson, Elin; Ferraris, Saima E.; He, Tao; Sahlgren, Cecilia; Eriksson, John E.

In: Molecular Biology of the Cell, Vol. 22, No. 9, 2011, p. 1539-1549.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Pallari, Hanna-Mari

AU - Lindqvist, Julia

AU - Torvaldson, Elin

AU - Ferraris, Saima E.

AU - He, Tao

AU - Sahlgren, Cecilia

AU - Eriksson, John E.

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AB - Many types of progenitor cells are distinguished by the expression of the intermediate filament protein nestin, a frequently used stem cell marker, the physiological roles of which are still unknown. Whereas myogenesis is characterized by dynamically regulated nestin levels, we studied how altering nestin levels affects myoblast differentiation. Nestin determined both the onset and pace of differentiation. Whereas depletion of nestin by RNAi strikingly accelerated the process, overexpression of nestin completely inhibited differentiation. Nestin down-regulation augmented the early stages of differentiation, at the level of cell-cycle withdrawal and expression of myogenic markers, but did not affect proliferation of undifferentiated dividing myoblasts. Nestin regulated the cleavage of the Cdk5 activator protein p35 to its degradation-resistant form, p25. In this way, nestin has the capacity to halt myoblast differentiation by inhibiting sustained activation of Cdk5 by p25, which is critical for the progress of differentiation. Our results imply that nestin regulates the early stages of myogenesis rather than maintains the undifferentiated state of progenitor cells. In the bidirectional interrelationship between nestin and Cdk5, Cdk5 regulates the organization and stability of its own nestin scaffold, which in turn controls the effects of Cdk5. This nestin–Cdk5 cross-talk sets the pace of muscle differentiation.

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JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

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Pallari H-M, Lindqvist J, Torvaldson E, Ferraris SE, He T, Sahlgren C et al. Nestin as a regulator of Cdk5 in differentiating myoblasts. Molecular Biology of the Cell. 2011;22(9):1539-1549. https://doi.org/10.1091/mbc.E10-07-0568