| RRC ID |
28845
|
| 著者 |
Sieglitz F, Matzat T, Yuva-Aydemir Y, Neuert H, Altenhein B, Klämbt C.
|
| タイトル |
Antagonistic feedback loops involving Rau and Sprouty in the Drosophila eye control neuronal and glial differentiation.
|
| ジャーナル |
Sci Signal
|
| Abstract |
During development, differentiation is often initiated by the activation of different receptor tyrosine kinases (RTKs), which results in the tightly regulated activation of cytoplasmic signaling cascades. In the differentiation of neurons and glia in the developing Drosophila eye, we found that the proper intensity of RTK signaling downstream of fibroblast growth factor receptor (FGFR) or epidermal growth factor receptor required two mutually antagonistic feedback loops. We identified a positive feedback loop mediated by the Ras association (RA) domain-containing protein Rau that sustained Ras activity and counteracted the negative feedback loop mediated by Sprouty. Rau has two RA domains that together showed a binding preference for GTP (guanosine 5'-triphosphate)-loaded (active) Ras. Rau homodimerized and was found in large-molecular weight complexes. Deletion of rau in flies decreased the differentiation of retinal wrapping glia and induced a rough eye phenotype, similar to that seen in alterations of Ras signaling. Further, the expression of sprouty was repressed and that of rau was increased by the COUP transcription factor Seven-up in the presence of weak, but not constitutive, activation of FGFR. Together, our findings reveal another regulatory mechanism that controls the intensity of RTK signaling in the developing neural network in the Drosophila eye.
|
| 巻・号 |
6(300)
|
| ページ |
ra96
|
| 公開日 |
2013-11-5
|
| DOI |
10.1126/scisignal.2004651
|
| PII |
6/300/ra96
|
| PMID |
24194583
|
| MeSH |
Animals
Blotting, Western
COUP Transcription Factors / metabolism
Cell Differentiation / physiology*
DNA-Binding Proteins / metabolism
Drosophila / embryology*
Drosophila Proteins / metabolism*
Enzyme Activation / physiology
Eye / cytology
Eye / embryology*
Feedback, Physiological / physiology*
Gene Expression Regulation / genetics
Gene Expression Regulation / physiology
Immunohistochemistry
In Situ Hybridization
Intracellular Signaling Peptides and Proteins / metabolism*
Membrane Proteins / metabolism
Microscopy, Electron, Transmission
Neuroglia / metabolism
Protein Binding
Protein Structure, Tertiary
Receptor Protein-Tyrosine Kinases / metabolism*
Receptors, Steroid / metabolism
Signal Transduction / physiology*
|
| IF |
6.467
|
| 引用数 |
20
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
|
