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A net-like structure with pores is observed during cell fusion induced by the receptor FGFRL1

机译:在受体FGFRL1诱导的细胞融合过程中观察到带有孔的网状结构

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FGFRL1 is the fifth member of the fibroblast growth factor receptor (FGFR) family. Similar to the other members, it harbors three Ig loops in its extracellular domain, but in contrast to the other receptors, it lacks the intracellular protein tyrosine kinase domain that would be required for signaling by transphosphorylation. FGFRL1 is mainly found in the musculoskeletal system, where it appears to inhibit cell proliferation but to induce cell adhesion and differentiation. Mice with a targeted disruption of the FGFRL1 gene die during birth due to a malformed diaphragm muscle, which is not strong enough to inflate the lungs after birth. Expression of FGFRL1 is highly up-regulated during the differentiation of myoblasts to multinucleated myotubes, suggesting an important role for FGFRL1 in cell-cell fusion. Recently we showed that FGFRL1 does indeed induce fusion of cultured cells into large syncytia. A reporter gene assay demonstrated that the third Ig domain and the transmembrane domain of FGFRL1 are both necessary and sufficient to fuse CHO cells into syncytia comprising several hundred nuclei. At the contact site, the fusing cells reveal a peculiar net-like structure with pores of about 1 μm diameter. It is possible that these structures represent membrane areas with fusion pores that set in motion the cell-cell fusion process. FGFRL1 is the first mammalian protein that is capable of triggering cell-cell fusion in vitro.
机译:FGFRL1是成纤维细胞生长因子受体(FGFR)家族的第五个成员。与其他成员相似,它在其细胞外结构域中具有三个Ig环,但与其他受体相比,它缺少通过转磷酸化进行信号传递所需的细胞内蛋白酪氨酸激酶结构域。 FGFRL1主要存在于肌肉骨骼系统中,似乎可以抑制细胞增殖,但可以诱导细胞粘附和分化。具有定向破坏性FGFRL1基因的小鼠在出生时因diaphragm肌畸形而死亡,diaphragm肌的强度不足以在出生后使肺膨胀。在成肌细胞分化为多核肌管的过程中,FGFRL1的表达高度上调,表明FGFRL1在细胞-细胞融合中的重要作用。最近,我们表明FGFRL1确实确实诱导了培养细胞融合成大合胞体。记者基因检测表明,FGFRL1的第三个Ig结构域和跨膜结构域对于将CHO细胞融合到包含数百个核的合胞体中都是必需的。在接触部位,融合细胞显示出具有约1μm直径的孔的特殊网状结构。这些结构可能代表带有融合孔的膜区域,而融合孔使细胞-细胞融合过程开始运动。 FGFRL1是第一个能够在体外触发细胞融合的哺乳动物蛋白。

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