TY  - INPR
A1  - Sánchez, María Florencia
A1  - Dietz, Marina
A1  - Müller, Ulrike
A1  - Weghuber, Julian
A1  - Gatterdam, Karl
A1  - Wieneke, Ralph
A1  - Heilemann, Mike
A1  - Lanzerstorfer, Peter
A1  - Tampé, Robert
T1  - Dynamic in situ confinement triggers ligand-free neuropeptide receptor signaling
T2  - bioRxiv
N2  - Membrane receptors are central to cell-cell communication. Receptor clustering at the plasma membrane modulates physiological responses, and mesoscale receptor organization is critical for downstream signaling. Spatially restricted cluster formation of the neuropeptide Y2 hormone receptor (Y2R) was observed in vivo; however, the relevance of this confinement is not fully understood. Here, we controlled Y2R clustering in situ by a chelator nanotool. Due to the multivalent interaction, we observed a dynamic exchange in the microscale confined regions. Fast Y2R enrichment in clustered areas triggered a ligand-independent downstream signaling determined by an increase in cytosolic calcium, cell spreading, and migration. We revealed that the cell response to ligand-induced activation was amplified when cells were pre-clustered by the nanotool. Ligand-independent signaling by clustering differed from ligand-induced activation in the binding of arrestin-3 as downstream effector, which was recruited to the confined regions only in the presence of the ligand. This approach enables in situ clustering of membrane receptors and raises the possibility to explore different modalities of receptor activation.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72986
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-729868
IS  - 2021.12.15.472742
ER  -