by Keyword: optopharmacology
Matera, Carlo, Calvé, Pablo, Casadó-Anguera, Verònica, Sortino, Rosalba, Gomila, Alexandre MJ., Moreno, Estefanía, Gener, Thomas, Delgado-Sallent, Cristina, Nebot, Pau, Costazza, Davide, Conde-Berriozabal, Sara, Masana, Mercè, Hernando, Jordi, Casadó, Vicent, Puig, MVictoria, Gorostiza, Pau, (2022). Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals International Journal Of Molecular Sciences 23, 10114
Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.
JTD Keywords: behavior, brainwave, d-1, dopamine, gpcr, in vivo electrophysiology, inhibitors, optogenetics, optopharmacology, photochromism, photopharmacology, photoswitch, stimulation, zebrafish, Azobenzene, Receptors
Gomila, Alexandre M. J., Rustler, Karin, Maleeva, Galyna, Nin-Hill, Alba, Wutz, Daniel, Bautista-Barrufet, Antoni, Rovira, Xavier, Bosch, Miquel, Mukhametova, Elvira, Petukhova, Elena, Ponomareva, Daria, Mukhamedyarov, Marat, Peiretti, Franck, Alfonso-Prieto, Mercedes, Rovira, Carme, König, Burkhard, Bregestovski, Piotr, Gorostiza, Pau, (2020). Photocontrol of endogenous glycine receptors in vivo Cell Chemical Biology 27, (11), 1425-1433.e7
Glycine receptors (GlyRs) are indispensable for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. Here we have developed Glyght, a GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understanding inhibitory circuits in intact animals and to developing drug-based phototherapies.
JTD Keywords: Glycine receptors, Photopharmacology, Optopharmacology, Inhibitory neurotransmission, CNS, Photoswitch
Gorostiza, Pau, Arosio, Daniele, Bregestovski, Piotr, (2013). Molecular probes and switches for functional analysis of receptors, ion channels and synaptic networks Frontiers in Molecular Neuroscience 6, (Article 48), 1-2
Nevola, L., Martín-Quirós, A., Eckelt, K., Camarero, N., Tosi, S., Llobet, A., Giralt, E., Gorostiza, P., (2013). Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis Angewandte Chemie - International Edition 52, (30), 7704-7708
Control of membrane traffic: Photoswitchable inhibitors of protein-protein interactions were applied to photoregulate clathrin-mediated endocytosis (CME) in living cells. Traffic light (TL) peptides acting as "stop" and "go" signals for membrane traffic can be used to dissect the role of CME in receptor internalization and in cell growth, division, and differentiation.
JTD Keywords: Clathrin-mediated endocytosis, Optopharmacology, Peptides, Photoswitches, Protein-protein interactions