Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2
Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2
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DOI：
10.1095/biolreprod.108.069765
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Chen, Hungwen
中科院分区：
文献类型：
--
作者：
Chen, Chie-Pein;Chen, Liang-Fu;Chen, Hungwen
细胞滋养层与多核合体滋养层的融合对于功能性胎盘的发育是必不可少的。人类内源性逆转录病毒W（HERV-W）家族成员合胞素1的包膜蛋白已被证明介导胎盘细胞融合。最近，另一种HERV家族成员（HERV-FRD）的包膜蛋白合胞素2已被鉴定并显示在胎盘中高度表达。为了更好地了解合胞素2的生物学，在这项研究中，我们首先研究了合胞素2基因在正常和先兆子痫胎盘中的表达，然后表征了合胞素2的功能。合胞素2基因的表达在先兆子痫胎盘中降低，并且可以被cAMP刺激剂forskolin刺激。内切蛋白酶弗林蛋白酶被发现参与合胞素1和2多肽的翻译后切割成表面和跨膜亚基。此外，由于合胞素1和2的亚基交换不能产生融合嵌合体，因此合胞素1和2的亚基的适当结合可能是每种蛋白质的功能完整性所必需的。最后，我们证明了在合胞素1和2中发现的形成二硫桥的CX 2C和CX 7 C基序对于它们的融合活性是必不可少的，因为CX 2C基序中的突变不仅废除了融合作用，而且还作为显性负突变体发挥作用。我们的研究结果表明，合胞素2可能作为胎盘细胞融合的第二个融合蛋白。
Fusion of cytotrophoblasts into the multinucleated syncytiotrophoblast layer is essential for the development of a functional placenta. The envelope protein of a human endogenous retrovirus W (HERV-W) family member, syncytin 1, has been shown to mediate placental cell fusion. Recently, the envelope protein of another HERV family member (HERV-FRD), syncytin 2, has been identified and shown to be highly expressed in the placenta. To better understand the biology of syncytin 2, in this study we first investigated syncytin 2 gene expression in normal and preeclamptic placentas and then characterized the functions of syncytin 2. The expression of syncytin 2 gene was decreased in preeclamptic placentas and could be stimulated by the cAMP stimulant forskolin. The endoprotease furin was found to be involved in the posttranslational cleavage of syncytin 1 and 2 polypeptides into surface and transmembrane subunits. in addition, proper association of the subunits of syncytins 1 and 2 is probably required for the functional integrity of each protein, because subunit swapping of syncytins 1 and 2 failed to generate fusogenic chimeras. Finally, we demonstrated that the disulfide bridge-forming CX2C and CX7C motifs found in syncytins 1 and 2 are essential for their fusogenic activities, because mutations in the CX2C motif not only abolished fusogenesis but also functioned as dominant-negative mutants. Our results suggest that syncytin 2 may function as a second fusogenic protein for placental cell fusion.