TY  - JOUR
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  - Nano letters
N2  - Membrane receptor clustering is fundamental to cell–cell communication; however, the physiological function of receptor clustering in cell signaling remains enigmatic. Here, we developed a dynamic platform to induce cluster formation of neuropeptide Y2 hormone receptors (Y2R) in situ by a chelator nanotool. The multivalent interaction enabled a dynamic exchange of histidine-tagged Y2R within the clusters. Fast Y2R enrichment in clustered areas triggered ligand-independent signaling as determined by an increase in cytosolic calcium and cell migration. Notably, the calcium and motility response to ligand-induced activation was amplified in preclustered cells, suggesting a key role of receptor clustering in sensitizing the dose response to lower ligand concentrations. Ligand-independent versus ligand-induced signaling differed in the binding of arrestin-3 as a downstream effector, which was recruited to the clusters only in the presence of the ligand. This approach allows in situ receptor clustering, raising the possibility to explore different receptor activation modalities.
KW  - G protein-coupled receptors
KW  - membrane organization
KW  - receptor dynamics
KW  - receptor condensates
KW  - phase separation
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73284
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-732848
SN  - 1530-6992
SN  - 1530-6984
VL  - 22
IS  - 20
SP  - 8363
EP  - 8371
PB  - American Chemical Society
CY  - Washington, DC
ER  -