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

Ryan G Walker; Tommaso Poggioli; Lida Katsimpardi; Sean M Buchanan; Juhyun Oh; Sam Wattrus; Bettina Heidecker; Yick W Fong; Lee L Rubin; Peter Ganz; Thomas B Thompson; Amy J Wagers; Richard T Lee

doi:10.1161/CIRCRESAHA.116.308391

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

Circ Res. 2016 Apr 1;118(7):1125-41; discussion 1142. doi: 10.1161/CIRCRESAHA.116.308391.

Authors

Affiliations

¹ From the Department of Molecular Genetics, College of Medicine, University of Cincinnati, OH (R.G.W., T.B.T.); Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (T.P., L.K., S.M.B., J.O., S.W., L.L.R., A.J.W., R.T.L.); Department of Neuroscience, Institut Pasteur, Paris, France (L.K.); Cardiovascular Division (T.P.), Department of Medicine, Brigham Regenerative Medicine Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.W.F., R.T.L.); Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA (J.O., S.W., A.J.W.); Division of Cardiology, Universitäres Herzzentrum, Zürich, Switzerland (B.H.); Department of Medicine, University of California, San Francisco (B.H., P.G.); and Division of Cardiology, San Francisco General Hospital, CA (P.G.).
² From the Department of Molecular Genetics, College of Medicine, University of Cincinnati, OH (R.G.W., T.B.T.); Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (T.P., L.K., S.M.B., J.O., S.W., L.L.R., A.J.W., R.T.L.); Department of Neuroscience, Institut Pasteur, Paris, France (L.K.); Cardiovascular Division (T.P.), Department of Medicine, Brigham Regenerative Medicine Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.W.F., R.T.L.); Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA (J.O., S.W., A.J.W.); Division of Cardiology, Universitäres Herzzentrum, Zürich, Switzerland (B.H.); Department of Medicine, University of California, San Francisco (B.H., P.G.); and Division of Cardiology, San Francisco General Hospital, CA (P.G.). [email protected] [email protected].

Abstract

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.

Keywords: heart disease; ligands; muscle; myocardium.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Adult
Aging / physiology
Amino Acid Sequence
Animals
Bone Morphogenetic Proteins / chemistry
Bone Morphogenetic Proteins / deficiency
Bone Morphogenetic Proteins / physiology*
Brain / growth & development
Brain / physiology
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
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

Substances

Bone Morphogenetic Proteins
FST protein, human
Follistatin
Follistatin-Related Proteins
Fstl3 protein, human
GDF11 protein, human
Gdf11 protein, mouse
Gdf11 protein, rat
Growth Differentiation Factors
MSTN protein, human
Mstn protein, mouse
Myostatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding