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Fecha
2025-08-12
Derechos de acceso
info:eu-repo/semantics/openAccess
Título de la revista
ISSN de la revista
Título del volumen
Editorial
Nature Research
Citas
Resumen
Clathrin-mediated endocytosis (CME), the main mechanism for swift, selective protein uptake in eukaryotic cells, initiates with adaptor protein AP2 recruitment to the plasma membrane (PM). AP2 recognizes PM-associated PtdIns(4,5)P2 and protein cargo for internalization. Nonetheless, many aspects of this process remain unclear due to their in vivo complexity. Here, a thermodynamic and time-resolved structural analysis of AP2 binding to different biomimetic PM was undertaken under physiological conditions using a combination of neutron reflectometry, interfacial tensiometry and rheology, and atomic force microscopy. The resultant in vitro data replicated previous in vivo observations, as well as yielded biophysical insights into normal and aborted CME. The presence of cargo may not be pivotal for the “activating” conformational change of AP2. However, the presence of cargo extends AP2’s residence time on the membrane surface, due to slower on- and off-rates, thereby tentatively giving sufficient time for CME to proceed fully. Moreover, upon interaction with AP2, phospholipid lateral diffusion decreases markedly, inducing a gel phase attributed to creating a percolated network involving AP2 on the membrane, which could potentially serve as a mechanism for modulating subsequent clathrin binding. The subsequent clathrin polymerization at the membrane is dependent on the AP2’s clathrin binding sequence.
Descripción
The registered version of this article, first published in “Communications Biology 8 (2025), 1196", is available online at the publisher's website: Nature Research, https://doi.org/10.1038/s42003-025-08597-5
La versión registrada de este artículo, publicado por primera vez en “Communications Biology 8 (2025), 1196", está disponible en línea en el sitio web del editor: Nature Research, https://doi.org/10.1038/s42003-025-08597-5
La versión registrada de este artículo, publicado por primera vez en “Communications Biology 8 (2025), 1196", está disponible en línea en el sitio web del editor: Nature Research, https://doi.org/10.1038/s42003-025-08597-5
Categorías UNESCO
Palabras clave
Citación
Maestro, A., Zaccai, N.R., Gonzalez-Martinez, J.F. et al., (2025). Combined thermodynamic and time-resolved structural analysis of interactions between AP2 and biomimetic plasma membranes provides insights into clathrin-mediated endocytosis. Commun Biol 8, 1196. https://doi.org/10.1038/s42003-025-08597-5
Centro
Facultad de Ciencias
Departamento
Física Interdisciplinar
Grupo de investigación
Grupo de investigación de materia blanda y fluidos