The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands.
The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands.
复制标题
DOI：
10.1083/jcb.200503113
复制
发表时间：
2005-09-12
期刊：
影响因子：
--
通讯作者：
Weinmaster G
中科院分区：
文献类型：
--
作者：
Ladi E;Nichols JT;Ge W;Miyamoto A;Yao C;Yang LT;Boulter J;Sun YE;Kintner C;Weinmaster G
DSL (Delta, Serrate, Lag2) Notch (N)配体Delta-样（Dll） 3的突变导致脊柱脊柱发育不良的骨骼异常，这与N信号在体细胞发生过程中的关键作用是一致的。DSL配体激活和抑制N信号的报道使理解Dll3的功能变得复杂。与其他DSL配体相比，我们发现Dll3在多个实验中不激活N信号。与这些发现一致，Dll3不与表达四种N受体中的任何一种的细胞结合，N1也不与表达Dll3的细胞结合。然而，与其他DSL配体一样，Dll3以细胞自主的方式抑制N信号传导。因此，Dll3的功能不像以前报道的那样是作为激活剂，而是作为N信号的专用抑制剂。Dll3作为一种N拮抗剂，促进非洲爪蟾神经发生，抑制小鼠神经祖细胞的胶质分化。最后，与调制极端分子一起，Dll3改变了由其他DSL配体诱导的N信号水平。
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.
登录
查看更多内容
影响因子：
4.2
作者：
Ge, WH;Martinowich, K;Sun, YE
通讯作者：
Sun, YE
影响因子：
64.5
作者：
LINDSELL, CE;SHAWBER, CJ;WEINMASTER, G
通讯作者：
WEINMASTER, G
影响因子：
30.8
作者：
Bulman, MP;Kusumi, K;Turnpenny, PD
通讯作者：
Turnpenny, PD
影响因子：
2.7
作者：
Bush, G;diSibio, G;Weinmaster, G
通讯作者：
Weinmaster, G
影响因子：
64.8
作者：
Hermanson, O;Jepsen, K;Rosenfeld, MG
通讯作者：
Rosenfeld, MG