| First Author | Acosta-Ruiz A | Year | 2020 |
| Journal | Neuron | Volume | 105 |
| Issue | 3 | Pages | 446-463.e13 |
| PubMed ID | 31784287 | Mgi Jnum | J:330682 |
| Mgi Id | MGI:6728222 | Doi | 10.1016/j.neuron.2019.10.036 |
| Citation | Acosta-Ruiz A, et al. (2020) Branched Photoswitchable Tethered Ligands Enable Ultra-efficient Optical Control and Detection of G Protein-Coupled Receptors In Vivo. Neuron 105(3):446-463.e13 |
| abstractText | The limitations of classical drugs have spurred the development of covalently tethered photoswitchable ligands to control neuromodulatory receptors. However, a major shortcoming of tethered photopharmacology is the inability to obtain optical control with an efficacy comparable with that of the native ligand. To overcome this, we developed a family of branched photoswitchable compounds to target metabotropic glutamate receptors (mGluRs). These compounds permit photo-agonism of Gi/o-coupled group II mGluRs with near-complete efficiency relative to glutamate when attached to receptors via a range of orthogonal, multiplexable modalities. Through a chimeric approach, branched ligands also allow efficient optical control of Gq-coupled mGluR5, which we use to probe the spatiotemporal properties of receptor-induced calcium oscillations. In addition, we report branched, photoswitch-fluorophore compounds for simultaneous receptor imaging and manipulation. Finally, we demonstrate this approach in vivo in mice, where photoactivation of SNAP-mGluR2 in the medial prefrontal cortex reversibly modulates working memory in normal and disease-associated states. |
