Manipulation of CD98 expression affects both trophoblast cell fusion and amino acid transport activity during syncytialization of human placental BeWo cells.
The physiological importance of CD98 surface antigen in regulating placental trophoblast cell fusion and amino acid transport activity has been studied in parallel in a cell model of syncytialization (the cytotrophoblast cell line BeWo following increased intracellular cAMP by forskolin treatment) using antisense oligonucleotides. CD98 protein abundance (determined by Western blot) was decreased by 50 % following antisense oligonucleotide transfection. Transfection with antisense oligonucleotide altered the responses of BeWo to forskolin. Cell fusion (determined by a quantitative flow cytometry assay) was inhibited by 57 %, and both human chorionic gonadotropin secretion and L-leucine influx through system L were suppressed. These findings show that CD98 is involved in the process of cell fusion necessary for syncytiotrophoblast formation and that during this physiologically important event, amino acid transport activity is also regulated through expression of this membrane protein.
Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX and Nuffield Department of Obstetrics and Gynecology, John Radcliffe Hospital, Oxford, UK.
Yoshiki
Y
Kudo
C A R
CA
Boyd
J
J
Millo
I L
IL
Sargent
C W G
CW
Redman
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D015153:Blotting, Western; D002459:Cell Fusion; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D027261:Fusion Regulatory Protein-1 / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents; D007930:Leucine / Q000493:pharmacokinetics; D008164:Luminescent Proteins; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D014162:Transfection; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D026905:Amino Acid Transport Systems; D006063:Chorionic Gonadotropin; D027261:Fusion Regulatory Protein-1; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D049452:Green Fluorescent Proteins; D005576:Colforsin; D000242:Cyclic AMP; D007930:Leucine