Light-dependent inhibition of clathrin-mediated endocytosis in yeast unveils conserved functions of the AP2 complex

Journal article

Summary: Clathrin-mediated endocytosis (CME) is an essential cellular process, conserved among eukaryotes. Yeast constitutes a powerful genetic model to dissect the complex endocytic machinery, yet there is a lack of specific pharmacological agents to interfere with CME in these organisms. TL2 is a light-regulated peptide inhibitor targeting the AP2-β-adaptin/β-arrestin interaction and that can photocontrol CME with high spatiotemporal precision in mammalian cells. Here, we study endocytic protein dynamics by live-cell imaging of the fluorescently tagged coat-associated protein Sla1-GFP, demonstrating that TL2 retains its inhibitory activity in S. cerevisiae spheroplasts. This is despite the β-adaptin/β-arrestin interaction not being conserved in yeast. Our data indicate that the AP2 α-adaptin is the functional target of activated TL2. We identified as interacting partners for the α-appendage, the Eps15 and epsin homologues Ede1 and Ent1. This demonstrates that endocytic cargo loading and sensing can be executed by conserved molecular interfaces, regardless of the proteins involved

Authors: Prischich, D; Camarero, N; Encinar Del Dedo, J; Cambra-Pellejà, M; Prat, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: iScience
• Volume: 26
• Issue: 10
• Pages: 107899-107899
• Publication date: 2023-09-12
• DOI: 10.1016/j.isci.2023.107899
• EISSN: 2589-0042
• ISSN: 2589-0042
• Language: English
• Keywords: Signal transducing adaptor protein; Signal transduction; Endocytic cycle; Clathrin; Cell biology; Endocytosis; Biochemistry; Receptor-mediated endocytosis; Biology; Yeast; Saccharomyces cerevisiae; Cell