Dynamic <i>in Situ</i> Confinement Triggers Ligand-Free Neuropeptide Receptor Signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36219818.
- Also identified by DOI 10.1021/acs.nanolett.2c03506 and PMC identifier 9614963.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 Y<sub>2</sub> hormone receptors (Y<sub>2</sub>R) <i>in situ</i> by a chelator nanotool. The multivalent interaction enabled a dynamic exchange of histidine-tagged Y<sub>2</sub>R within the clusters. Fast Y<sub>2</sub>R 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 <i>in situ</i> receptor clustering, raising the possibility to explore different receptor activation modalities.
Medical subject headings
- Neuropeptide Y
- Histidine