A role for fibronectin-leucine-rich transmembrane cell-surface proteins in homotypic cell adhesion
A role for fibronectin-leucine-rich transmembrane cell-surface proteins in homotypic cell adhesion
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DOI：
10.1038/sj.embor.7400614
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发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Niehrs, C
中科院分区：
文献类型：
--
作者：
Karaulanov, EE;Böttcher, RT;Niehrs, C
富含亮氨酸重复序列 (LRR) 蛋白的纤连蛋白富含亮氨酸跨膜 (FLRT) 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。在这里，我们分析了 FLRT 是否也可能在细胞粘附中发挥作用。我们发现 FLRT 蛋白可以发生物理相互作用，并且 FLRT 转染的培养细胞与未转染的细胞分选出来，这表明粘附特性发生了变化。在爪蟾胚胎和组织聚集体中也观察到类似的分选效应。 FLRT 介导的细胞分选是钙依赖性和底物依赖性的。删除分析表明细胞分选需要 LRR 结构域，而 LRR 结构域对于 FLRT 介导的 FGF 信号传导来说是可有可无的。相反，分选独立于细胞质结构域，而细胞质结构域对于 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可以在分子上解偶联。结果表明 FLRT 蛋白具有双重作用，促进 FGF 信号传导和调节同型细胞粘附。
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.