Receptor usage of Syncytin-1: ASCT2, but not ASCT1, is a functional receptor and effector of cell fusion in the human placenta

• 成果类型: Article
• 署名作者: Stafl, Krystof; Travnicek, Martin; Janovska, Anna; Kucerova, Dana; Pecnova, Lubomira; Yang, Zhiqi; Stepanec, Vladimir; Jech, Lukas; Salker, Madhuri S.; Hejnar, Jiri; Trejbalova, Katerina
• 署名单位: Czech Academy of Sciences; Institute of Molecular Genetics of the Czech Academy of Sciences; Czech Academy of Sciences; Institute of Molecular Genetics of the Czech Academy of Sciences; Eberhard Karls University of Tubingen
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13655
• DOI: 10.1073/pnas.2407519121
• 发表日期: 2024-10-29
• 关键词: amino-acid transporter; herv-w; envelope glycoprotein; rd-114 virus; endogenous retroviruses; expression; feline; infection; protein; methylation

摘要

Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental syncytiotrophoblast formation. To mediate cell- to- cell fusion, Syncytin-1 requires specific interaction with its cognate receptor. Two trimeric transmembrane proteins, Alanine, Serine, Cysteine Transporters 1 and 2 (ASCT1 and ASCT2), were suggested and widely accepted as Syncytin-1 cellular receptors. To quantitatively assess the individual contributions of human ASCT1 and ASCT2 to the fusogenic activity of Syncytin-1, we developed a model system where the ASCT1 and ASCT2 double knockout was rescued by ectopic expression of either ASCT1 or ASCT2. We demonstrated that ASCT2 was required for Syncytin-1 binding, cellular entry, and cell- to- cell fusion, while ASCT1 was not involved in this receptor interaction. We experimentally validated the ASCT1- ASCT2 heterotrimers as a possible explanation for the previous misidentification of ASCT1 as a receptor for Syncytin-1. This redefinition of receptor specificity is important for proper understanding of Syncytin-1 function in normal and pathological pregnancy.