Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells
Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells
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DOI：
10.1016/j.bbamcr.2015.05.027
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发表时间：
2015-10-01
影响因子：
5.1
通讯作者：
Trueb, Beat
中科院分区：
文献类型：
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作者：
Zhuang, Lei;Pandey, Amit V.;Trueb, Beat
FGFRL1是一种单遍跨膜蛋白，具有三个细胞外Ig结构域。当在CHO细胞或相关细胞类型中过表达时，它诱导细胞间融合并形成大的多核合胞体。对于这种促进融合的活性，只需要膜近端Ig结构域（Ig3）和跨膜结构域。跨膜结构域是来自FGFRL1还是来自其他受体并不重要，但Ig3结构域与膜的距离至关重要。含有Ig1-Ig2-Ig3或Ig2-Ig3结构域的可溶性重组蛋白以及针对Ig3的单克隆抗体可以抑制融合。突变分析显示Ig3中存在融合所需的疏水位点。如果这个位点的一个氨基酸发生突变，融合就会终止。正如FGFRL1三维结构的计算机建模所预测的那样，该位点位于β -薄片上，该薄片是更大β -桶的一部分。这个位点可能与邻近细胞的靶蛋白相互作用，从而触发细胞-细胞融合。(C) 2015 Elsevier B.V.版权所有
FGFRL1 is a single-pass transmembrane protein with three extracellular Ig domains. When overexpressed in CHO cells or related cell types, it induces cell-cell fusion and formation of large, multinucleated syncytia. For this fusion-promoting activity, only the membrane-proximal Ig domain (Ig3) and the transmembrane domain are required. It does not matter whether the transmembrane domain is derived from FGFRL1 or from another receptor, but the distance of the Ig3 domain to the membrane is crucial. Fusion can be inhibited with soluble recombinant proteins comprising the Ig1-Ig2-Ig3 or the Ig2-Ig3 domains as well as with monoclonal antibodies directed against Ig3. Mutational analysis reveals a hydrophobic site in Ig3 that is required for fusion. If a single amino acid from this site is mutated, fusion is abolished. The site is located on a beta-sheet, which is part of a larger beta-barrel, as predicted by computer modeling of the 3D structure of FGFRL1. It is possible that this site interacts with a target protein of neighboring cells to trigger cell-cell fusion. (C) 2015 Elsevier B.V. All rights reserved.