Sep 24 – 28, 2023
Faculty of Physics, Astronomy and Applied Computer Science; Jagiellonian University
Europe/Warsaw timezone
Lectures will take place in A1-03 hall (see

Catalytically optimized search strategy

Sep 25, 2023, 2:40 PM
Faculty of Physics, Astronomy and Applied Computer Science; Jagiellonian University

Faculty of Physics, Astronomy and Applied Computer Science; Jagiellonian University

Lojasiewicza 11 30-348 Kraków Poland
Regular Talk Session 4


Dr Yann Lanoiselée (Basque Center for Applied Mathematics)


Understanding how information is transmitted from the exterior to the interior of living cells is essential for developing new therapeutic strategies. Despite recent structural advances, the mechanisms that govern interactions of membrane-bound receptors with intracellular arrestin molecules at the plasma membrane remain elusive. Here [1], we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in b-arrestin interactions with both receptors and the lipid bilayer.

We carefully characterize the spatiotemporal co-dynamics of receptors and arrestins. We show that receptor and arrestin diffusion has multiple states that are linked to biological function.

Unexpectedly, our results reveal that b-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 b-arrestin in a longer-lived membrane-bound state, allowing it to diffuse to clathrin-coated pits separately from the activating receptor.

This constitutes a new mechanism for the target-search strategy that combines surface-mediated diffusion with catalytic activation.

These results open the way to new questions in search strategies and expand our current understanding of b-arrestin function at the plasma membrane.

[1] Lanoiselée, Grimes, Koszegi et al.
Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell. 2023

Primary authors

Dr Yann Lanoiselée (Basque Center for Applied Mathematics) Dr Jak Grimes (University of Birmingham) Dr Zsombor Koszegi (University of Birmingham)


Dr Tamara Miljus (University of Birmingham) Dr Shannon O'Brien (University of Birmingham) Dr Tomasz Stepniewski (Pompeu Fabra University) Dr Brian Medel-Lacruz (Pompeu Fabra University) Dr Mithu Baidya (Indian Institute of Technology) Dr Maria Makarova (University of Birmingham) Mr Ravi Mistry (University of Birmingham) Dr Joelle Goulding (University of Notthingham) Dr Julia Drube (Jena University) Prof. Carsten Hoffman (Jena University) Prof. Dylan Owen (University of Birmingham) Prof. Arun Shukla (IIT Kanpur) Prof. Jana Selent (University of Barcelona) Prof. Stephen Hill (University of Birmingham) Prof. Davide Calebiro (University of Birmingham)

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