Regulation of muscle differentiation and survival by Acheron

Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA 01003, USA.
Mechanisms of development (Impact Factor: 2.44). 06/2009; 126(8-9):700-9. DOI: 10.1016/j.mod.2009.05.003
Source: PubMed


Acheron (Achn), a phylogenetically-conserved member of the Lupus antigen family of RNA binding proteins, was initially identified as a novel cell death-associated gene from the intersegmental muscles of the tobacco hawkmoth Manduca sexta. C(2)C(12) cells are a standard model for the study of myogenesis. When deprived of growth factors, these cells can be induced to: form multinucleated myotubes, arrest as quiescent satellite-like reserve cells, or undergo apoptosis. Achn expression is induced in myoblasts that form myotubes and acts upstream of the muscle specific transcription factor MyoD. Forced expression of ectopic Achn resulted in the formation of larger myotubes and massive reserve cell death relative to controls. Conversely, dominant-negative or antisense Achn blocked myotube formation following loss of growth factors, suggesting that Achn plays an essential, permissive role in myogenesis. Studies in zebrafish embryos support this hypothesis. Reduction of Achn with antisense morpholinos led to muscle fiber loss and an increase in the number of surviving cells in the somites, while ectopic Achn enhanced muscle fiber formation and reduced cell numbers. These results display a crucial evolutionarily conserved role for Achn in myogenesis and suggest that it plays key roles in the processes of differentiation and self-renewal.

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Available from: Lawrence M Schwartz, Aug 16, 2014
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    • "As a consequence, the elongation phase of polymerase II is slowed down and transcription becomes inefficient. In contrast, LARP6 (also termed Acheron) interacts with Id transcription factors as well as CASK (calcium/calmodulin-dependent serine protein kinase) and has been linked to apoptosis (Valavanis et al. 2007; Wang et al. 2009; Weng et al. 2009). A regulatory effect on type I collagen mRNA translation by LARP6 has also been reported recently (Cai et al. 2010). "
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    ABSTRACT: Acheron (Achn) was originally identified as novel gene that is induced when insect muscles become committed to die at the end of metamorphosis. In separate studies, we have demonstrated that Achn acts upstream of MyoD and is required by mammalian myoblasts to either differentiate or undergo apoptosis following loss of growth factors. In the present study we examined the role of Achn in regulating integrin-extracellular matrix interactions that are required for myogenesis. Both control C2C12 myoblasts and those engineered to express ectopic Achn expressed the fibronectin receptor integrin alpha(5)beta(1) in the presence of growth factors and the laminin receptor alpha(7)beta(1) following growth factor withdrawal. Expression of the laminin receptor was blocked in cells expressing either Achn antisense or an Achn deletion mutant that blocks differentiation. Control cells and those expressing ectopic Achn undergo sequential and transient increases in both substrate adhesion and migration before cell fusion. Blockade of Achn expression reduced these effects on laminin but not on fibronectin. Taken together, these data suggest that Achn may influence differentiation in part via its control of cell adhesion dynamics.
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