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

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-reg...

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Detalhes bibliográficos
Autores: Prischich, Davia, Camarero, Núria, Encinar del Dedo, Javier, Cambra-Pellejà, Maria, Prat, Judit, Nevola, Laura, Martín-Quirós, Andrés, Rebollo, Elena, Pastor, Laura, Giralt, Ernest, Geli, María Isabel, Gorostiza, Pau
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/351363
Acesso em linha:http://hdl.handle.net/10261/351363
https://api.elsevier.com/content/abstract/scopus_id/85172229133
Access Level:acceso abierto
Palavra-chave:Biochemistry
Biological sciences
Cell biology
Molecular biology
Natural sciences
Descrição
Resumo: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.