Functional characterization of the human placental fusogenic membrane protein syncytin 2.
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.
Chen
Chie-Pein
CP
Division of High Risk Pregnancy and Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan.
Chen
Liang-Fu
LF
Yang
Su-Ray
SR
Chen
Chia-Yu
CY
Ko
Chun-Chuan
CC
Chang
Geen-Dong
GD
Chen
Hungwen
H
D016022:Case-Control Studies; D002459:Cell Fusion; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D045683:Furin / Q000378:metabolism; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000378:metabolism; D006801:Humans; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
C518353:ERVFRD-1 protein, human; D020536:Enzyme Activators; D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin; D005576:Colforsin; D045683:Furin