Karaulanov Emil E, Böttcher Ralph T, Niehrs Christof
Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
EMBO Rep. 2006 Mar;7(3):283-90. doi: 10.1038/sj.embor.7400614. Epub 2006 Jan 20.
The fibronectin-leucine-rich transmembrane (FLRT) family of leucine-rich repeat (LRR) proteins is implicated in fibroblast growth factor (FGF) signalling, early embryonic development and neurite outgrowth. Here, we have analysed whether FLRTs may also function in cell adhesion. We find that FLRT proteins can physically interact and that FLRT-transfected cultured cells sort out from non-transfected cells, suggesting a change in adhesive properties. A similar sorting effect is also observed in Xenopus embryos and tissue aggregates. FLRT-mediated cell sorting is calcium dependent and substrate independent. Deletion analysis indicates that cell sorting requires the LRR domains, which are dispensable for FLRT-mediated FGF signalling. Conversely, sorting is independent of the cytoplasmic domain, which is essential for FLRT-induced signalling. Therefore, FLRT-mediated FGF signal transduction and homotypic cell sorting can be molecularly uncoupled. The results indicate that FLRT proteins have a dual role, promoting FGF signalling and modulating homotypic cell adhesion.
富含亮氨酸重复序列(LRR)的纤连蛋白-富含亮氨酸跨膜(FLRT)蛋白家族与成纤维细胞生长因子(FGF)信号传导、早期胚胎发育和神经突生长有关。在此,我们分析了FLRTs是否也在细胞黏附中发挥作用。我们发现FLRT蛋白能够发生物理相互作用,并且转染了FLRT的培养细胞会与未转染的细胞分离,这表明黏附特性发生了变化。在非洲爪蟾胚胎和组织聚集体中也观察到了类似的分选效应。FLRT介导的细胞分选是钙依赖性的且不依赖于底物。缺失分析表明细胞分选需要LRR结构域,而这对于FLRT介导的FGF信号传导是可有可无的。相反,分选不依赖于细胞质结构域,而该结构域对于FLRT诱导的信号传导至关重要。因此,FLRT介导的FGF信号转导和同型细胞分选在分子水平上可以解偶联。结果表明,FLRT蛋白具有双重作用,即促进FGF信号传导和调节同型细胞黏附。