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: 2.83). 06/2009; 126(8-9):700-9. DOI: 10.1016/j.mod.2009.05.003
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: RNA binding protein acheron has proved to be either the mediator of integrin-extracellular matrix interactions or the regulatory factor that participates in vertebrate development, cell differentiation and cell death. We report the role of acheron in vascular endothelial proliferation, angiogenesis and wound healing post-trauma. Co-immunoprecipitation showed that Acheron forms a ternary complex with β1 integrin and Id1 in human umbilical vein endothelial cells following stimulation with serious trauma serum. Acheron, vascular endothelial growth factor (VEGF), and β1 integrin mRNA expression was apparently inhibited, and capillary density and wound healing rate also were reduced in Id1-deficient mice trauma model. Acheron together with Id1 significantly induces VEGF, not CD105 level inhibition by serious trauma serum for 24 h. In conclusion, we have demonstrated that acheron may be an effective mediator of promoting endothelial proliferation, angiogenesis and wound healing probably by regulating VEGF together with Id1.
    Cell Biochemistry and Function 12/2011; 29(8):636-40. DOI:10.1002/cbf.1799 · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The fusion of one cell with another occurs in development, injury and disease. Despite the diversity of fusion events, five steps in sequence appear common. These steps include programming fusion-competent status, chemotaxis, membrane adhesion, membrane fusion, and post-fusion resetting. Recent advances in the field start to reveal the molecules involved in each step. This review focuses on some key molecules and cellular events of cell fusion in mammals. Increasing evidence demonstrates that membrane lipid rafts, adhesion proteins and actin rearrangement are critical in the final step of membrane fusion. Here we propose a new model for the formation and expansion of membrane fusion pores based on recent observations on myotube formation. In this model, membrane lipid rafts first recruit adhesion molecules and align with opposing membranes, with the help of a cortical actin "wall" as a rigid supportive platform. Second, the membrane adhesion proteins interact with each other and trigger actin rearrangement, which leads to rapid dispersion of lipid rafts and flow of a highly fluidic phospholipid bilayer into the site. Finally, the opposing phospholipid bilayers are then pushed into direct contact leading to the formation of fusion pores by the force generated through actin polymerization. The actin polymerization generated force also drives the expansion of the fusion pores. However, several key questions about the process of cell fusion still remain to be explored. The understanding of the mechanisms of cell fusion may provide new opportunities in correcting development disorders or regenerating damaged tissues by inhibiting or promoting molecular events associated with fusion.
    Advances in Experimental Medicine and Biology 01/2011; 713:33-64. DOI:10.1007/978-94-007-0763-4_4 · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The La-related proteins (LARPs) form a diverse group of RNA-binding proteins characterized by the possession of a composite RNA binding unit, the La module. The La module comprises two domains, the La motif (LaM) and the RRM1, which together recognize and bind to a wide array of RNA substrates. Structural information regarding the La module is at present restricted to the prototypic La protein, which acts as an RNA chaperone binding to 3' UUUOH sequences of nascent RNA polymerase III transcripts. In contrast, LARP6 is implicated in the regulation of collagen synthesis and interacts with a specific stem-loop within the 5' UTR of the collagen mRNA. Here, we present the structure of the LaM and RRM1 of human LARP6 uncovering in both cases considerable structural variation in comparison to the equivalent domains in La and revealing an unprecedented fold for the RRM1. A mutagenic study guided by the structures revealed that RNA recognition requires synergy between the LaM and RRM1 as well as the participation of the interdomain linker, probably in realizing tandem domain configurations and dynamics required for substrate selectivity. Our study highlights a considerable complexity and plasticity in the architecture of the La module within LARPs. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 12/2014; 43(1). DOI:10.1093/nar/gku1287 · 8.81 Impact Factor

Full-text (2 Sources)

Available from
Aug 16, 2014