Nestin as a regulator of Cdk5 in differentiating myoblasts

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Pallari, Lindqvist, Torvaldson, Ferraris, He, Sahlgren, Eriksson
Förläggare: American Society for Cell Biology
Publiceringsår: 2011
Tidskrift: Molecular Biology of the Cell
Tidskriftsakronym: Mol Biol Cell
Volym: 22
Nummer: 9
Artikelns första sida, sidnummer: 1539
Artikelns sista sida, sidnummer: 1549
ISSN: 1939-4586
eISSN: 1939-4586


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.

Senast uppdaterad 2020-19-01 vid 03:25