| RRC ID |
46118
|
| 著者 |
Honnen SJ, Büchter C, Schröder V, Hoffmann M, Kohara Y, Kampkötter A, Bossinger O.
|
| タイトル |
C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.
|
| ジャーナル |
PLoS One
|
| Abstract |
The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.
|
| 巻・号 |
7(2)
|
| ページ |
e32183
|
| 公開日 |
2012-1-1
|
| DOI |
10.1371/journal.pone.0032183
|
| PII |
PONE-D-11-17701
|
| PMID |
22359667
|
| PMC |
PMC3281126
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / physiology*
Cell Polarity
Forkhead Transcription Factors
Heat-Shock Response
Insulin / metabolism*
Insulin-Like Growth Factor I / metabolism*
Longevity*
Oxidative Stress
Phosphoproteins / genetics
Phosphoproteins / physiology*
RNA, Small Interfering / pharmacology
Receptor, Insulin
Signal Transduction*
Transcription Factors
|
| IF |
2.74
|
| 引用数 |
7
|
|
WOS 分野
|
MULTIDISCIPLINARY SCIENCES
|
| リソース情報 |
| 線虫 |
tm1422 |
