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

Kód výsledku v 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>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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