Presenilin-1 acts via Id1 to regulate the function of muscle satellite cells in a γ-secretase-independent manner

Yusuke Ono, Viola F. Gnocchi, Peter S. Zammit, Ryoichi Nagatomi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Muscle satellite cells are the resident stem cells of adult skeletal muscle. Here, we have examined the role of the multifunctional protein presenilin-1 (PS1) in satellite cell function. PS1 acts as a crucial component of the γ-secretase complex, which is required to cleave single-pass transmembrane proteins such as Notch and amyloid-β precursor protein. PS1, however, also functions through γ-secretase-independent pathways. Activation of satellite cells was accompanied by induction of PS1, with PS1 knockdown enhancing their myogenic differentiation, but reducing their self-renewal. Transfection with siRNA against PS1 led to accelerated myogenic differentiation during muscle regeneration in vivo. Conversely, constitutive expression of PS1 resulted in t he suppression of myogenic differentiation and promotion of the self-renewal phenotype. Importantly, we found that PS1 also acts independently of its role in γ-secretase activity in controlling myogenesis, which is mediated in part by Id1 (inhibitor of DNA binding 1), a negative regulator of the myogenic regulatory factor MyoD. PS1 can control Id1, which affects satellite cell fate by regulating the transcriptional activity of MyoD. Taken together, our observations show that PS1 is a key player in the choice of satellite cell fate, acting through both γ-secretase-dependent and γ-secretase-independent mechanisms.

本文言語English
ページ(範囲)4427-4438
ページ数12
ジャーナルJournal of cell science
122
24
DOI
出版ステータスPublished - 2009 12月 15
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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