Xenorhodopsin - a new inward-directed proton pump for an alternative optogentic approach

Scientists from the Max-Planck-Institute of Biophysics in Frankfurt report inward directed proton pumps of xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. The structure of a xenorhodopsin from the nanohalosarchaeon Nanosalina (NsXeR) revealed the ion translocation pathway to be different to currently known rhodopsins. NsXeR is a powerful pump with a high turnover rate that is able to elicit action potential up to the maximum intrinsic firing frequency. Light-induced depolarizing current by NsXeR was sufficient for the activation of neuronal rat hippocampal cells with high temporal accuracy. Important to note, NsXeR is entirely independent of ion conditions giving rise to an alternative for light-induced control of neurons as well to cation-selective channelrhodopsins.

Altogether these newly discovered inward directed proton pumps are a valuable new optogenetic tool, which is cation independent, pH insensitive and with highly specific activation capacity that can be expressed in a broad spectrum of cells. Xenorhodopsin can be used for the modification of cell organelles as well as for specific biomedical applications where precise subtle effects are needed.

Priority application was filed in March 2017 (WO2018189247). Nationalization in US, EP, JP, CA, and CN.

• Shevchenko, Vitaly, et al. "Inward H+ pump xenorhodopsin: Mechanism and alternative optogenetic approach." Science advances 3.9 (2017): e1603187.
• Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., & Bamberg, E.: Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 13940-13945. (2003). https://doi.org/10.1073/pnas.1936192100