| Autor: |
Kolesov DV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia., Ivanova VO; Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia., Sokolinskaya EL; Skolkovo Institute of Science and Technology, Moscow, Russia., Kost LA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia., Balaban PM; Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia., Lukyanov KA; Skolkovo Institute of Science and Technology, Moscow, Russia., Nikitin ES; Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia., Bogdanov AM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. noobissat@ya.ru. |
| Abstrakt: |
Insect odorant receptors (ORs) have been suggested to function as ligand-gated cation channels, with OrX/Orco heteromers combining ionotropic and metabotropic activity. The latter is mediated by different G proteins and results in Orco self-activation by cyclic nucleotide binding. In this contribution, we co-express the odor-specific subunits DmOr49b and DmOr59b with either wild-type Orco or an Orco-PKC mutant lacking cAMP activation heterologously in mammalian cells. We show that the characteristics of heteromers strongly depend on both the OrX type and the coreceptor variant. Thus, methyl acetate-sensitive Or59b/Orco demonstrated 25-fold faster response kinetics over o-cresol-specific Or49b/Orco, while the latter required a 10-100 times lower ligand concentration to evoke a similar electrical response. Compared to wild-type Orco, Orco-PKC decreased odorant sensitivity in both heteromers, and blocked an outward current rectification intrinsic to the Or49b/Orco pair. Our observations thus provide an insight into insect OrX/Orco functioning, highlighting their natural and artificial tuning features and laying the groundwork for their application in chemogenetics, drug screening, and repellent design. |
Full text from SpringerLink