A variant of human growth differentiation factor-9 that improves oocyte developmental competence
William A Stocker, Kelly L Walton, Dulama Richani, Karen L Chan, Kiri H Beilby, Bethany J Finger, Mark P Green, Robert B Gilchrist, Craig A Harrison
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2020
Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are co-expressed exclusively in oocytes throughout most of folliculogenesis and play central roles in controlling ovarian physiology. Although both growth factors exist as homodimers, recent evidence indicates that GDF9 and BMP15 can also heterodimerize to form the potent growth factor cumulin. Within the cumulin complex, BMP15 "activates" latent GDF9, enabling potent signaling in granulosa cells via type I receptors (i.e. activin receptor-like kinase-4/5 (ALK4/5)) and SMAD2/3 transcription factors. In the cumulin heterodimer, two distinct type I receptor interfaces are formed compared with homodimeric GDF9 and ..View full abstract
Awarded by National Institutes of Health
We thank Dr. David Mottershead (Keele University, United Kingdom) for providing the GDF9 and BMP15 expression vectors and Lesley Ritter (The University of Adelaide, Australia) for providing advice about the culture of mouse granulosa cells. The Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, CA, was supported by National Institutes of Health Grant P41 RR-01081.