| RRC ID |
80915
|
| 著者 |
DeGroot MS, Williams B, Chang TY, Maas Gamboa ML, Larus IM, Hong G, Fromme JC, Liu J.
|
| タイトル |
SMOC-1 interacts with both BMP and glypican to regulate BMP signaling in C. elegans.
|
| ジャーナル |
PLoS Biol
|
| Abstract |
Secreted modular calcium-binding proteins (SMOCs) are conserved matricellular proteins found in organisms from Caenorhabditis elegans to humans. SMOC homologs characteristically contain 1 or 2 extracellular calcium-binding (EC) domain(s) and 1 or 2 thyroglobulin type-1 (TY) domain(s). SMOC proteins in Drosophila and Xenopus have been found to interact with cell surface heparan sulfate proteoglycans (HSPGs) to exert both positive and negative influences on the conserved bone morphogenetic protein (BMP) signaling pathway. In this study, we used a combination of biochemical, structural modeling, and molecular genetic approaches to dissect the functions of the sole SMOC protein in C. elegans. We showed that CeSMOC-1 binds to the heparin sulfate proteoglycan GPC3 homolog LON-2/glypican, as well as the mature domain of the BMP2/4 homolog DBL-1. Moreover, CeSMOC-1 can simultaneously bind LON-2/glypican and DBL-1/BMP. The interaction between CeSMOC-1 and LON-2/glypican is mediated specifically by the EC domain of CeSMOC-1, while the full interaction between CeSMOC-1 and DBL-1/BMP requires full-length CeSMOC-1. We provide both in vitro biochemical and in vivo functional evidence demonstrating that CeSMOC-1 functions both negatively in a LON-2/glypican-dependent manner and positively in a DBL-1/BMP-dependent manner to regulate BMP signaling. We further showed that in silico, Drosophila and vertebrate SMOC proteins can also bind to mature BMP dimers. Our work provides a mechanistic basis for how the evolutionarily conserved SMOC proteins regulate BMP signaling.
|
| 巻・号 |
21(8)
|
| ページ |
e3002272
|
| 公開日 |
2023-8-1
|
| DOI |
10.1371/journal.pbio.3002272
|
| PII |
PBIOLOGY-D-23-00096
|
| PMID |
37590248
|
| PMC |
PMC10464977
|
| MeSH |
Animals
Biological Transport
Bone Morphogenetic Proteins* / metabolism
Caenorhabditis elegans
Caenorhabditis elegans Proteins* / metabolism
Calcium-Binding Proteins* / metabolism
Glypicans* / metabolism
Signal Transduction
|
| リソース情報 |
| 線虫 |
tm7125 |
