Hicks C, Johnston S H, diSibio G, Collazo A, Vogt T F, Weinmaster G
Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90095-1737, USA.
Nat Cell Biol. 2000 Aug;2(8):515-20. doi: 10.1038/35019553.
Proteins encoded by the fringe family of genes are required to modulate Notch signalling in a wide range of developmental contexts. Using a cell co-culture assay, we find that mammalian Lunatic fringe (Lfng) inhibits Jagged1-mediated signalling and potentiates Delta1-mediated signalling through Notch1. Lfng localizes to the Golgi, and Lfng-dependent modulation of Notch signalling requires both expression of Lfng in the Notch-responsive cell and the Notch extracellular domain. Lfng does not prevent binding of soluble Jagged1 or Delta1 to Notch1-expressing cells. Lfng potentiates both Jagged1- and Delta1-mediated signalling via Notch2, in contrast to its actions with Notch1. Our data suggest that Fringe-dependent differential modulation of the interaction of Delta/Serrate/Lag2 (DSL) ligands with their Notch receptors is likely to have a significant role in the combinatorial repertoire of Notch signalling in mammals.
边缘基因家族编码的蛋白质在广泛的发育环境中调节Notch信号传导时是必需的。通过细胞共培养试验，我们发现哺乳动物的 Lunatic fringe（Lfng）抑制Jagged1介导的信号传导，并通过Notch1增强Delta1介导的信号传导。Lfng定位于高尔基体，并且Lfng对Notch信号传导的调节需要Lfng在Notch反应性细胞中的表达以及Notch细胞外结构域。Lfng不会阻止可溶性Jagged1或Delta1与表达Notch1的细胞结合。与它对Notch1的作用相反，Lfng通过Notch2增强Jagged1和Delta1介导的信号传导。我们的数据表明，边缘蛋白对Delta/Serrate/Lag2（DSL）配体与其Notch受体相互作用的差异调节可能在哺乳动物Notch信号传导的组合模式中起重要作用。
