ZFIN ID: ZDB-PUB-140523-6
SCUBE3 (Signal Peptide-CUB-EGF Domain-containing Protein 3) Modulates Fibroblast Growth Factor Signaling during Fast Muscle Development
Tu, C.F., Tsao, K.C., Lee, S.J., Yang, R.B.
Date: 2014
Source: The Journal of biological chemistry   289(27): 18928-18942 (Journal)
Registered Authors: Lee, Shyh-Jye, Yang, Ruey-Bing (Ray)
Keywords: cell differentiation, fast muscle, fibroblast growth factor (FGF), fibroblast growth factor receptor (FGFR), myogenesis, scube3, zebrafish
MeSH Terms:
  • Animals
  • Calcium-Binding Proteins/deficiency
  • Calcium-Binding Proteins/genetics
  • Calcium-Binding Proteins/metabolism*
  • Cell Differentiation
  • Fibroblast Growth Factor 8/metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Glycoproteins/deficiency
  • Glycoproteins/genetics
  • Glycoproteins/metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Muscle Development*
  • MyoD Protein/metabolism
  • Oligonucleotides, Antisense/genetics
  • Phenotype
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptor, Fibroblast Growth Factor, Type 4/metabolism
  • Receptors, Cell Surface/deficiency
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism*
  • Signal Transduction*
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 24849601 Full text @ J. Biol. Chem.
SCUBE3 (signal peptide CUB-EGF-like domain-containing protein 3) belongs to a newly identified secreted and cell membrane-associated SCUBE family, which is evolutionarily conserved in vertebrates. Scube3 is predominantly expressed in a variety of developing tissues in mice such as somites, neural tubes, and limb buds. However, its function during development remains unclear. In this study, we first showed that knockdown of SCUBE3 in C2C12 myoblasts inhibited fibroblast growth factor receptor 4 (FGFR4) expression and FGF signaling, thus resulting in reduced myogenic differentiation. Furthermore, knockdown of zebrafish scube3 by antisense morpholino oligonucleotides specifically suppressed the expression of the myogenic marker myod1 within the lateral fast-muscle precursors, whereas its expression in the adaxial slow-muscle precursors was largely unaffected. Consistent with these findings, immunofluorescent staining of fast- but not slow-muscle myosin was markedly decreased in scube3 morphants. Further genetic studies identified fgf8 as a key regulator in scube3-mediated fast-muscle differentiation in zebrafish. Biochemical and molecular analysis showed that SCUBE3 acts as a FGF co-receptor to augment FGF8 signaling. Scube3 may be a critical upstream regulator of fast-fiber myogenesis by modulating fgf8 signaling during zebrafish embryogenesis.