Functional characterization of the human placental fusogenic membrane protein syncytin 2.

Published

Journal Article

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 CX(2)C and CX(7)C motifs found in syncytins 1 and 2 are essential for their fusogenic activities, because mutations in the CX(2)C 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.

Full Text

Cited Authors

  • Chen, C-P; Chen, L-F; Yang, S-R; Chen, C-Y; Ko, C-C; Chang, G-D; Chen, H

Published Date

  • November 2008

Published In

Volume / Issue

  • 79 / 5

Start / End Page

  • 815 - 823

PubMed ID

  • 18650494

Pubmed Central ID

  • 18650494

Electronic International Standard Serial Number (EISSN)

  • 1529-7268

International Standard Serial Number (ISSN)

  • 0006-3363

Digital Object Identifier (DOI)

  • 10.1095/biolreprod.108.069765

Language

  • eng