The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands
| Autor: | Weihong Ge, Ena Ladi, Jim Boulter, James T. Nichols, Chris Kintner, Yi E. Sun, Alison Miyamoto, Gerry Weinmaster, Liang-Tung Yang, Christine Yao |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Xenopus
Notch signaling pathway Embryonic Development Ligands medicine.disease_cause Article Cell Line Mice Xenopus laevis 03 medical and health sciences L Cells 0302 clinical medicine Tubulin Somitogenesis medicine Animals Biotinylation Luciferases Receptor Research Articles 030304 developmental biology Neurons Genetics 0303 health sciences Mutation biology Activator (genetics) Neurogenesis Intracellular Signaling Peptides and Proteins Glycosyltransferases Membrane Proteins Cell Biology biology.organism_classification Coculture Techniques Rats Cell biology NIH 3T3 Cells Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200503113 |
| Popis: | Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis. Understanding how Dll3 functions is complicated by reports that DSL ligands both activate and inhibit N signaling. In contrast to other DSL ligands, we show that Dll3 does not activate N signaling in multiple assays. Consistent with these findings, Dll3 does not bind to cells expressing any of the four N receptors, and N1 does not bind Dll3-expressing cells. However, in a cell-autonomous manner, Dll3 suppressed N signaling, as was found for other DSL ligands. Therefore, Dll3 functions not as an activator as previously reported but rather as a dedicated inhibitor of N signaling. As an N antagonist, Dll3 promoted Xenopus laevis neurogenesis and inhibited glial differentiation of mouse neural progenitors. Finally, together with the modulator lunatic fringe, Dll3 altered N signaling levels that were induced by other DSL ligands. |
| Databáze: | OpenAIRE |
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