Molecular requirements and regulation of syncytin (HERV-W env)-induced cell-cell fusion

• Applicant: Dr. Andy J.G. Pötgens
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2003 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5398585

We aim to elucidate the molecular mechanisms regulating cell-cell fusion induced by syncytin, the envelope protein of a human endogenous retrovirus, HERV-W. In the human, cell-cell fusion occurs during development of certain tissues: it is necessary for myotube formation, osteoclastogenesis and syncytiotrophoblast formation. The latter process depends on the fusogenic membrane protein syncytin. Its receptor is thought to be RDR, the receptor for type-D retroviruses, identical with the amino acid transporter ATB(0). We study the dependency of trophoblast cell fusion on local levels of syncytin and RDR. Our working hypotheses are based on knowledge about the roles of envelope-receptor interactions in virus-cell fusion (e.g. HIV-infection) and virus induced cell-cell fusion: 1) Trophoblast fusion is dependent on two fusion partners, one with a sufficient local expression of syncytin, the other expressing sufficient RDR. 2) Fusion can be inhibited by a) downregulation of either syncytin or RDR in one of the fusion partners, or b) through reciprocal blocking by upregulation of RDR in the syncytin-expressing partner or of syncytin in the RDR-expressing partner. These hypotheses will be tested in a sensitive two-color cell fusion assay using pairs of genetically engineered cell lines displaying differential levels of syncytin and RDR, and by IHC and TEM in tissue specimens of placental villi.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Peter Kaufmann (†)