Functional analysis of the placental fusogenic proteins,syncytin 1 and syncytin 2

• Main Authors: Liang-Fu Chen, 陳亮甫
• Other Authors: 陳宏文
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/13749671682706832785

碩士 === 國立臺灣大學 === 生化科學研究所 === 96 === Abstract Fusion of cytotrophoblast into the multinucleated syncytiotrophoblast layer is essential for the development of a functional placenta. Previous studies of placental development have shown that the envelope protein of a human endogenous retrovirus W (HERV-W), syncytin 1, may mediate placental cell fusion. Recently, the envelope protein of HERV-FRD, syncytin 2, has been identified and shown to be highly expressed in placenta. This implies that syncytin 2 may be involved in placental cell fusion. Our previous studies have demonstrated that the cytoplasmic domain (CTM) of syncytin 1 inhibits its fusogenic activity. In this study, we first tested whether the CTM of syncytin 2 regulates its fusogenic activity. We found that the CTM of syncytin 2 is required for its fusogenic activity. We further studied the biosynthesis of syncytins and demonstrated that Furin is involved in the proteolytic cleavage of syncytin 1 and syncytin 2 by using furin inhibitor and in the Furin-defective human colon carcinoma LoVo cell line. Finally, we studied the role of the disulfide-forming CXXC and CX6CC motifs in syncytins and found that the disulfide linkage between SU and TM subunits is essential for the fusogenic activity of syncytins because mutation in the CXXC motif abolishes the fusogenic activity of syncytins and causes a dominant-negative effect. Overall, this study provides a better understanding of the biology of syncytin 1 and syncytin 2.