Plasma membrane preassociation drives β-arrestin coupling to receptors and activation

Grimes, Jak; Koszegi, Zsombor; Lanoiselée, Yann; Miljus, Tamara; O'Brien, Shannon L.; Stepniewski, Tomasz Maciej, 1988-; Medel Lacruz, Brian; Baidya, Mithu; Makarova, Maria; Mistry, Ravi; Goulding, Joëlle; Drube, Julia; Hoffmann, Carsten; Owen, Dylan M.; Shukla, Arun K.; Selent, Jana; Hill, Stephen J.; Calebiro, Davide

Plasma membrane preassociation drives β-arrestin coupling to receptors and activation

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dc.contributor.author Grimes, Jak
dc.contributor.author Koszegi, Zsombor
dc.contributor.author Lanoiselée, Yann
dc.contributor.author Miljus, Tamara
dc.contributor.author O'Brien, Shannon L.
dc.contributor.author Stepniewski, Tomasz Maciej, 1988-
dc.contributor.author Medel Lacruz, Brian
dc.contributor.author Baidya, Mithu
dc.contributor.author Makarova, Maria
dc.contributor.author Mistry, Ravi
dc.contributor.author Goulding, Joëlle
dc.contributor.author Drube, Julia
dc.contributor.author Hoffmann, Carsten
dc.contributor.author Owen, Dylan M.
dc.contributor.author Shukla, Arun K.
dc.contributor.author Selent, Jana
dc.contributor.author Hill, Stephen J.
dc.contributor.author Calebiro, Davide
dc.date.accessioned 2023-09-08T06:28:01Z
dc.date.available 2023-09-08T06:28:01Z
dc.date.issued 2023
dc.description.abstract β-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-β-arrestin interactions at the plasma membrane of living cells remain elusive. Here, we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in β-arrestin interactions with both receptors and the lipid bilayer. Unexpectedly, our results reveal that β-arrestin spontaneously inserts into the lipid bilayer and transiently interacts with receptors via lateral diffusion on the plasma membrane. Moreover, they indicate that, following receptor interaction, the plasma membrane stabilizes β-arrestin in a longer-lived, membrane-bound state, allowing it to diffuse to clathrin-coated pits separately from the activating receptor. These results expand our current understanding of β-arrestin function at the plasma membrane, revealing a critical role for β-arrestin preassociation with the lipid bilayer in facilitating its interactions with receptors and subsequent activation.
dc.format.mimetype application/pdf
dc.identifier.citation Grimes J, Koszegi Z, Lanoiselée Y, Miljus T, O’Brien SL, Stepniewski TM, Medel-Lacruz B, Baidya M, Makarova M, Mistry R, Goulding J, Drube J, Hoffmann C, Owen DM, Shukla AK, Selent J, Hill SJ. Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell. 2023;186(10):2238-55. DOI: 10.1016/j.cell.2023.04.018
dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2023.04.018
dc.identifier.issn 0092-8674
dc.identifier.uri http://hdl.handle.net/10230/57839
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell. 2023;186(10):2238-55
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword G protein-coupled receptors
dc.subject.keyword GPCR
dc.subject.keyword TIRF
dc.subject.keyword Arrestin
dc.subject.keyword Plasma membrane
dc.subject.keyword Protein-protein interactions
dc.subject.keyword Single-molecule microscopy
dc.title Plasma membrane preassociation drives β-arrestin coupling to receptors and activation
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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