Similar sequences but dissimilar biological functions of GDF11 and myostatin

Abstract

Growth differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related TGFβ family members that are often believed to serve similar functions due to their high homology. However, genetic studies in animals provide clear evidence that they perform distinct roles. While the loss of Mstn leads to hypermuscularity, the deletion of Gdf11 results in abnormal skeletal patterning and organ development. The perinatal lethality of Gdf11-null mice, which contrasts with the long-term viability of Mstn-null mice, has led most research to focus on utilizing recombinant GDF11 proteins to investigate the postnatal functions of GDF11. However, the reported outcomes of the exogenous application of recombinant GDF11 proteins are controversial partly because of the different sources and qualities of recombinant GDF11 used and because recombinant GDF11 and MSTN proteins are nearly indistinguishable due to their similar structural and biochemical properties. Here, we analyze the similarities and differences between GDF11 and MSTN from an evolutionary point of view and summarize the current understanding of the biological processing, signaling, and physiological functions of GDF11 and MSTN. Finally, we discuss the potential use of recombinant GDF11 as a therapeutic option for a wide range of medical conditions and the possible adverse effects of GDF11 inhibition mediated by MSTN inhibitors.

Growth factors: untangling twin proteins

A growth factor protein called GDF11 has potential for rejuvenation of heart, brain, and muscle tissues, but first its relationship with a twin growth factor (MSTN) must be unraveled. Although GDF11 and MSTN are almost identical in amino acid sequence, MSTN controls growth of skeletal muscles, and GDF11 regulates bone and organ patterning. To untangle what differentiates these proteins, Yun-Sil Lee and Joonho Suh at Seoul National University, South Korea, reviewed their evolution and function. They report that GDF11 and MSTN are the result of duplication of an original gene and have evolved to perform different roles. They cover some of the beneficial effects reported with GDF11 supplementation, such as tissue rejuvenation and increased lifespan, but caution that negative effects have been reported. Further investigation may illuminate growth and development processes, and therapeutic potential.