論文 - 詳細
| RRC ID | 81260 |
|---|---|
| 著者 | Zhang P, Pronovost SM, Marchetti M, Zhang C, Kang X, Kandelouei T, Li C, Edgar BA. |
| タイトル | Inter-cell type interactions that control JNK signaling in the Drosophila intestine. |
| ジャーナル | Nat Commun |
| Abstract |
JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the Drosophila intestine, the TNF-type ligand, Eiger (Egr), is expressed exclusively by intestinal stem cells (ISCs) and enteroblasts (EBs), where it is induced by stress and during aging. Egr preferentially activates JNK signaling in a paracrine fashion in differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N-glycosylation genes (Alg3, Alg9) restrain this activation, and stress-induced downregulation of Alg3 and Alg9 correlates with JNK activation, suggesting a regulatory switch. JNK activity in ECs induces expression of the intermembrane protease Rhomboid (Rho), driving secretion of EGFR ligands Keren (Krn) and Spitz (Spi), which in turn activate EGFR signaling in progenitor cells (ISCs and EBs) to stimulate their growth and division, as well as to produce more Egr. This study uncovers an N-glycosylation-controlled, paracrine JNK-EGFR-JNK feedforward loop that sustains ISC proliferation during stress-induced gut regeneration. |
| 巻・号 | 15(1) |
| ページ | 5493 |
| 公開日 | 2024-6-28 |
| DOI | 10.1038/s41467-024-49786-w |
| PII | 10.1038/s41467-024-49786-w |
| PMID | 38944657 |
| PMC | PMC11214625 |
| MeSH | Animals Cell Communication Cell Differentiation Cell Proliferation Drosophila / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Enterocytes / cytology Enterocytes / metabolism Epidermal Growth Factor ErbB Receptors* / genetics ErbB Receptors* / metabolism Glycosylation Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Intestines* / cytology JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Signaling System* Membrane Proteins Receptors, Invertebrate Peptide / genetics Receptors, Invertebrate Peptide / metabolism Signal Transduction Stem Cells / cytology Stem Cells / metabolism |
| IF | 12.121 |
| リソース情報 | |
| ショウジョウバエ | 1395R-1 DGRC#109620 DGRC#109623 DGRC#109626 |