| RRC ID |
21997
|
| 著者 |
Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A, Nishimura T.
|
| タイトル |
A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila.
|
| ジャーナル |
Genes Dev
|
| Abstract |
Members of the insulin peptide family have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Drosophila insulin-like peptides (Dilps) promote tissue growth through the single insulin-like receptor (InR). Despite the important role of Dilps in nutrient-dependent growth control, the molecular mechanism that regulates the activity of circulating Dilps is not well understood. Here, we report the function of a novel secreted decoy of InR (SDR) as a negative regulator of insulin signaling. SDR is predominantly expressed in glia and is secreted into the hemolymph. Larvae lacking SDR grow at a faster rate, thereby increasing adult body size. Conversely, overexpression of SDR reduces body growth non-cell-autonomously. SDR is structurally similar to the extracellular domain of InR and interacts with several Dilps in vitro independent of Imp-L2, the ortholog of the mammalian insulin-like growth factor-binding protein 7 (IGFBP7). We further demonstrate that SDR is constantly secreted into the hemolymph independent of nutritional status and is essential for adjusting insulin signaling under adverse food conditions. We propose that Drosophila uses a secreted decoy to fine-tune systemic growth against fluctuations of circulating insulin levels.
|
| 巻・号 |
27(1)
|
| ページ |
87-97
|
| 公開日 |
2013-1-1
|
| DOI |
10.1101/gad.204479.112
|
| PII |
27/1/87
|
| PMID |
23307869
|
| PMC |
PMC3553286
|
| MeSH |
Animals
Drosophila Proteins / metabolism*
Drosophila melanogaster / growth & development*
Drosophila melanogaster / metabolism
Gene Expression Regulation, Developmental
Hemolymph / metabolism
Insulin / metabolism*
Larva
Neuroglia / metabolism
Receptor Protein-Tyrosine Kinases / metabolism
Signal Transduction*
Somatomedins / metabolism*
|
| IF |
9.527
|
| 引用数 |
60
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
DGRC#206122 |
