@article {70451,
	title = {The dark side of channelrhodopsins: intrinsic ion conductance of apo-opsins},
	journal = {Research Square},
	year = {2026},
	month = {2026 Jun 09},
	abstract = {<p>Opsins are known as proteins that bind retinal to form light-sensing rhodopsins, which mediate diverse forms of photoreception and are widely used for optogenetic control of cellular activity. Yet many opsins lack canonical retinal-binding features or, in their native biological contexts, are expressed where chromophore availability is limited, raising the question whether retinal-free opsins are silent. Here we show that retinal-free ion-transporting microbial opsins are not inert but adopt intrinsic, light-independent functional states alongside their canonical light-driven activity. Using developmental phenotyping in transgenic Drosophila melanogaster, electrophysiology in Xenopus oocytes and mammalian cells, together with structural and computational analyses, we demonstrate robust light-independent ion conductance in multiple channel-type opsins and an ion-pumping opsin. Structural modeling and molecular dynamics simulations reveal conformational rearrangements in transmembrane helices and internal water networks that are consistent with stabilization of apo-conductive states. Together, these findings establish apo-opsin activity as a defined functional state of microbial opsins, expand the current framework of rhodopsin biology, and highlight the need to consider chromophore-independent activity in both basic research and optogenetic applications.</p>
},
	doi = {10.21203/rs.3.rs-9039624/v1},
	url = {https://www.doi.org10.21203/rs.3.rs-9039624/v1},
	author = {Gao, Shiqiang and Zhang, Chong and Ma, Jie and Fukuda, Masahiro and Lin, Yiechang and Zhu, Mo and Duan, Xiao and Zhou, Lingbo and Zettner, Maximilian and Yang, Shang and Wang, Yanhui and Yu-Strzelczyk, Jing and Zheng, Qiang and Dannh{\"a}user, Sven and Kobayashi, Kazuhiro and Tajima, Seiya and Nakamura, Seiwa and Kim, Suhyang and Takeno, Yuka and Gee, Christine and Shi, Jiachen and He, Yuge and Kittel, Robert and Heckmann, Manfred and Nagel, Georg and Shen, Yin and Cory, Ben and Kato, Hideaki}
}
@article {69483,
	title = {It only takes seconds for a human monoclonal autoantibody to inhibit N-methyl-D-aspartate receptors},
	journal = {bioRxiv},
	year = {2024},
	month = {2024 Jun 01},
	abstract = {<p>Transfer of autoantibodies targeting ionotropic N-methyl-D-aspartate receptors in autoimmune encephalitis patients into mice leads to typical disease signs. Long-term effects of the pathogenic antibodies consist of immunoglobulin G-induced crosslinking and receptor internalization. We focused on the direct and immediate impact of a specific pathogenic patient-derived monoclonal autoantibody (immunoglobulin G $\#$003-102) on receptor function.We performed cell-attached recordings in cells transfected with the GluN1 and GluN2A subunit of the N-methyl-D-aspartate receptor. Immunoglobulin G $\#$003-102 binds to the amino-terminal domain of the glycine-binding GluN1 subunit. It reduced simultaneous receptor openings significantly compared to controls at both low and high glutamate and glycine concentrations. Closer examination of our data in 50-second to 2-second intervals revealed, that Immunoglobulin G $\#$003-102 rapidly decreases the number of open receptors. However, antigen-binding fragments of immunoglobulin G $\#$003-102 did not reduce the receptor openings.In conclusion, patient-derived immunoglobulin G $\#$003-102 inhibits N-methyl-D-aspartate receptors rapidly and directly before receptor internalization occurs and the entire immunoglobulin G is necessary for this acute inhibitory effect. This suggests an application of the antigen-binding fragment-like constructs of $\#$003-102 as a potential new treatment strategy for shielding the pathogenic epitopes on the N-methyl-D-aspartate receptors.</p>
},
	doi = {10.1101/2024.05.28.595700},
	url = {https://www.biorxiv.org/content/early/2024/06/01/2024.05.28.595700},
	author = {Yang, Shang and Heckmann, Johanna and Taha, Abdulla and Gao, Shiqiang and Steinke, Stephan and Hust, Michael and Pr{\"u}{\ss}, Harald and Furukawa, Hiro and Geis, Christian and Heckmann, Manfred and Yu-Strzelczyk, Jing}
}
