ASCT1 as a specific cellular receptor for . Syncytin-1 and other endogenous retroviruses

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00580797" target="_blank" >RIV/68378050:_____/23:00580797 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

ASCT1 as a specific cellular receptor for . Syncytin-1 and other endogenous retroviruses

Original language description

syncytin-1 is a human protein-coding gene of retroviral origin. During human placenta morphogenesis, the interaction of Syncytin-1 with the transmembrane protein ASCT2 (Alanine, Serine, Cysteine Transporter 2) triggers cell-to-cell fusion of trophoblasts, resulting in the formation of a syncytiotrophoblast, a large multinucleated syncytium. The syncytiotrophoblast is the outermost surface of the human placenta. Altered behavior of Syncytin-1 may contribute to human placenta pathologies, including preeclampsia, low platelet syndrome/intrauterine growth restriction. ASCT1, a sodium-dependent neutral amino acid transporter with a related structure to ASCT2, was postulated as an alternative Syncytin-1 cellular receptor. Furthermore, both ASCT1 and ASCT2 have been reported to be receptors for the largest interference group, the RD114-and D-type (RDR) retroviruses. The contribution of both receptors to Syncytin-1-induced cell-cell fusion, as well as the receptor preference of RDR retroviruses, remain to be understood. In this study, we investigated the individual involvement of each receptor in the interaction with Syncytin-1 using three quantitative molecular assays. We measured the infection with the Syncytin-1-pseudotyped virus triggered by the ASCT2 or ASCT1 receptors independently. Further, we assessed the binding of Syncytin-1 to ASCT2 vs. ASCT1 on the cell surface. Finally, we determined the Syncytin-1 fusogenic activityninduced by the interaction with ASCT2 or ASCT1 . Our results demonstrate that ASCT1 is at least two orders of magnitude less active as a receptor than ASCT2, which casts doubt on the importance of ASCT1 for syncytiotrophoblast differentiation. These findings highlight the function of ASCT2 during placental development and challenge the physiological role of ASCT1 during Syncytin-1-induced fusion.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů