Proceedings of The Physiological Society

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC111

Poster Communications

Myostatin and its downstream signalling pathways are well maintained between Mus musculus and Homo sapiens

B. T. Elliott1, D. Renshaw1, S. Getting1, R. Mackenzie1

1. School of Life Sciences, University of Westminster, London, United Kingdom.

Skeletal muscle is key in the maintenance of homeostasis in humans; atrophy of muscle has negative health effects. A significant regulator of muscle mass is the myostatin signalling pathway (McPherron et al., 1997), which inhibits anabolism and myoblast proliferation, and promotes catabolism via multiple signalling pathways (reviewed by Elliott et al., 2012). In muscle research, the mouse C2C12 myoblast line is widely used, as derived by Yaffe and Saxel (1977). A frequent critique of research utilizing animal cell lines is the relevance of findings to human physiology in vivo. We therefore aimed to examine the relevance of results arising from use of the C2C12 cell line to translational work. Specifically, we chose to examine the evidence of protein homology of myostatin, its receptors, and its downstream intracellular signalling pathways between mouse and human. Protein basic local alignment search tool (pBLAST) was used to assess homology (NCBI; Altschul et al., 1997). As well as myostatin and its receptor pair, activin receptor 2B (ARIIB) and activin receptor 1B (Alk 4), the targeted proteins were the smad2, smad3, smad4 of the myoblast proliferation inhibition pathway, FoxO1, atrogin and murf of the proteasomal pathway and Akt, mTOR and, GSK-3b, p70s6k and 4EBP-1 of the pro-anabolic pathway. BLAST protein-protein analysis revealed significant percentage identity between human and mouse myostatin proteins (96% similarity) and significantly, 100% conservation of myostatin's bioactive C-terminus. This similarity is decreased in other common research models. For example, myostatin from Danio rerio (Zebrafish) shows only 68% similarity when compared to human, with an 86% similarity in the C-terminus region. Homology is conserved in both receptor components, ARIIB (94%) and Alk 4 (98%). Smad signalling is well conserved, with smad2, smad3 and smad4 sharing 99%, 99% and 97% identity to the compared human proteins, respectively. The FoxO1-atrogin-murf signalling pathway is similarly well conserved, with 91%, 95% and 93% identity, respectively to the human homologues. Akt and mTOR share 88% and 99% sequence identity respectively, while p70S6k, GSK-3B and 4E-BP1 show 99%, 99% and 91% sequence identity, respectively.

Where applicable, experiments conform with Society ethical requirements