Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1539-1549 |
| Journal | Molecular Biology of the Cell |
| Volume | 22 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2011 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- intermediate filaments
- nestin
- Cdk5 signaling
- p35
- muscle differentiation
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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 journal › Article › Scientific › peer-review
TY - JOUR
T1 - Nestin as a regulator of Cdk5 in differentiating myoblasts
AU - Pallari, Hanna-Mari
AU - Lindqvist, Julia
AU - Torvaldson, Elin
AU - Ferraris, Saima E.
AU - He, Tao
AU - Sahlgren, Cecilia
AU - Eriksson, John E.
PY - 2011
Y1 - 2011
N2 - 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.
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.
KW - intermediate filaments
KW - nestin
KW - Cdk5 signaling
KW - p35
KW - muscle differentiation
U2 - 10.1091/mbc.E10-07-0568
DO - 10.1091/mbc.E10-07-0568
M3 - Article
VL - 22
SP - 1539
EP - 1549
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 9
ER -