RRC ID |
39422
|
著者 |
Matsunaga Y, Gengyo-Ando K, Mitani S, Iwasaki T, Kawano T.
|
タイトル |
Physiological function, expression pattern, and transcriptional regulation of a Caenorhabditis elegans insulin-like peptide, INS-18.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
In Caenorhabditis elegans, insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an important pathway that controls larval diapause and adult lifespan. The IIS pathway is modulated by many insulin-like peptides (ILPs) through the DAF-2 receptor, the sole insulin/IGF-1 receptor-like protein in C. elegans. We previously identified the ILP, INS-18, and predicted its tertiary structure to be similar to the crystal structures of human insulin and IGF-1. In this study, the physiological function of INS-18 was first examined by gene disruption and overexpression, and we identified INS-18 as a DAF-2 antagonist required for larval diapause and longevity. Analysis of the INS-18 expression pattern using a reporter gene showed it to be expressed in nerve cells, including hermaphrodite-specific neurons (HSNs) at the adult stage. Other ILP expressions have not been previously observed in HSNs, and we believe that INS-18 expression in these cells may contribute to longevity by regulating reproduction. Loss of the DAF-16 transcription factor located downstream of the IIS pathway completely blocked ins-18 expression. We propose a positive feedback model for the regulation of ins-18 expression in which an antagonist binding to the DAF-2 receptor increases ins-18 gene expression, thus leading to increased INS-18 protein levels and increased DAF-2 receptor binding. Thus, this study provides a new insight into the hormonal regulation of insulin, an important and widespread process in the animal kingdom.
|
巻・号 |
423(3)
|
ページ |
478-83
|
公開日 |
2012-7-6
|
DOI |
10.1016/j.bbrc.2012.05.145
|
PII |
S0006-291X(12)01044-3
|
PMID |
22683638
|
MeSH |
Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / growth & development
Caenorhabditis elegans Proteins / antagonists & inhibitors
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Forkhead Transcription Factors
Gene Expression Regulation*
Larva / genetics
Larva / growth & development
Longevity / genetics
Neurons / metabolism*
Peptide Hormones / genetics*
RNA Interference
Receptor, Insulin / antagonists & inhibitors
Receptor, Insulin / genetics
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription, Genetic*
|
IF |
2.985
|
引用数 |
21
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
線虫 |
tm339
tm1907 |