Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation

Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating...

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Bibliographic Details
Published in:Circulation research 2016-04, Vol.118 (7), p.1125-1142
Main Authors: Walker, Ryan G, Poggioli, Tommaso, Katsimpardi, Lida, Buchanan, Sean M, Oh, Juhyun, Wattrus, Sam, Heidecker, Bettina, Fong, Yick W, Rubin, Lee L, Ganz, Peter, Thompson, Thomas B, Wagers, Amy J, Lee, Richard T
Format: Article
Language:English
Subjects:
Adult
Aging - physiology
Amino Acid Sequence
Animals
Bone Morphogenetic Proteins - chemistry
Bone Morphogenetic Proteins - deficiency
Bone Morphogenetic Proteins - physiology
Brain - growth & development
Brain - physiology
Cellular Biology
Dimerization
Female
Follistatin - metabolism
Follistatin-Related Proteins - metabolism
Growth Differentiation Factors - chemistry
Growth Differentiation Factors - deficiency
Growth Differentiation Factors - physiology
Growth Differentiation Factors - therapeutic use
Heart - physiology
Heart Diseases - metabolism
Humans
Life Sciences
Male
Mice
Models, Molecular
Molecular Sequence Data
Muscles - physiology
Myocardium - metabolism
Myostatin - chemistry
Myostatin - deficiency
Myostatin - physiology
Organ Specificity
Protein Conformation
Protein Structure, Tertiary
Rats
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction
Structure-Activity Relationship
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Summary:Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging.
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.116.308391