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BOR - Papers in Press, published online ahead of print July 23, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.069765
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BIOLOGY OF REPRODUCTION 79, 815–823 (2008)
DOI: 10.1095/biolreprod.108.069765
© 2008 by the Society for the Study of Reproduction, Inc.

Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 21

Chie-Pein Chen 3 4, Liang-Fu Chen 5, Su-Ray Yang 5, Chia-Yu Chen 4, Chun-Chuan Ko 4, Geen-Dong Chang 5, and Hungwen Chen 2 5 6

Division of High Risk Pregnancy3 and Department of Medical Research,4 Mackay Memorial Hospital, Taipei 104, Taiwan Graduate Institute of Biochemical Sciences,5 National Taiwan University, Taipei 106, Taiwan Institute of Biological Chemistry,6 Academia Sinica, Nankang, Taipei 115, Taiwan

ABSTRACT

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..

cell fusion, placenta, pregnancy, syncytin 1, syncytin 2, syncytiotrophoblast, trophoblast


FOOTNOTES

1Supported by grants to H.C. from the National Science Council of Taiwan (grant 96-2311-B-001-034), National Taiwan University (grant 95R0066-BM06-02), and Academia Sinica of Taiwan, and to C.-P. C. from the National Science Council of Taiwan (grant 95-2314-B-195-018) and the Mackay Memorial Hospital (MMH-E-97001).

Correspondence: 2FAX: 011 886 2 27889759; e-mail: hwchen{at}gate.sinica.edu.tw




This article has been cited by other articles:


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M.-H. Chiang, F.-Y. Liang, C.-P. Chen, C.-W. Chang, M.-L. Cheong, L.-J. Wang, C.-Y. Liang, F.-Y. Lin, C.-C. Chou, and H. Chen
Mechanism of Hypoxia-induced GCM1 Degradation: IMPLICATIONS FOR THE PATHOGENESIS OF PREECLAMPSIA
J. Biol. Chem., June 26, 2009; 284(26): 17411 - 17419.
[Abstract] [Full Text] [PDF]




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