SMOC can act as both an antagonist and an expander of BMP signaling.
The matricellular protein SMOC (Secreted Modular Calcium binding protein) is conserved phylogenetically from vertebrates to arthropods. We showed previously that SMOC inhibits bone morphogenetic protein (BMP) signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In contrast, the most prominent effect of theDrosophilaorthologue,pentagone(pent), is expanding the range of BMP signaling during wing patterning. Using SMOC deletion constructs we found that SMOC-∆EC, lacking the extracellular calcium binding (EC) domain, inhibited BMP2 signaling, whereas SMOC-EC (EC domain only) enhanced BMP2 signaling. The SMOC-EC domain bound HSPGs with a similar affinity to BMP2 and could expand the range of BMP signaling in an in vitro assay by competition for HSPG-binding. Together with data from studies in vivo we propose a model to explain how these two activities contribute to the function of Pent inDrosophilawing development and SMOC in mammalian joint formation.
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
J Terrig
0000-0001-9252-1011
JT
Thomas
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
D
D
Eric Dollins
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
Kristin R
KR
Andrykovich
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
Tehyen
T
Chu
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
Brian G
BG
Stultz
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
Deborah A
DA
Hursh
Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, U.S. Food and Drug Administration, Silver Spring, United States.
Malcolm
M
Moos
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007596:Joints / Q000196:embryology; D051379:Mice; D009024:Morphogenesis; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
C504610:Bmp2 protein, Xenopus; D055396:Bone Morphogenetic Protein 2; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; C562078:Magu protein, Drosophila; D015676:Osteonectin; C543141:SMOC1 protein, Xenopus; D029867:Xenopus Proteins
BMP Signaling; D. melanogaster; SMOC; developmental biology; drosophila wing; evolutionary biology; genomics; skeletal joint; stem cells; xenopus