| First Author | Brown J | Year | 2018 |
| Journal | Cell | Volume | 175 |
| Issue | 4 | Pages | 1131-1140.e11 |
| PubMed ID | 30343901 | Mgi Jnum | J:268640 |
| Mgi Id | MGI:6259394 | Doi | 10.1016/j.cell.2018.09.026 |
| Citation | Brown J, et al. (2018) Expanding the Optogenetics Toolkit by Topological Inversion of Rhodopsins. Cell 175(4):1131-1140.e11 |
| abstractText | Targeted manipulation of activity in specific populations of neurons is important for investigating the neural circuit basis of behavior. Optogenetic approaches using light-sensitive microbial rhodopsins have permitted manipulations to reach a level of temporal precision that is enabling functional circuit dissection. As demand for more precise perturbations to serve specific experimental goals increases, a palette of opsins with diverse selectivity, kinetics, and spectral properties will be needed. Here, we introduce a novel approach of "topological engineering"-inversion of opsins in the plasma membrane-and demonstrate that it can produce variants with unique functional properties of interest for circuit neuroscience. In one striking example, inversion of a Channelrhodopsin variant converted it from a potent activator into a fast-acting inhibitor that operates as a cation pump. Our findings argue that membrane topology provides a useful orthogonal dimension of protein engineering that immediately permits as much as a doubling of the available toolkit. |
