Imaging and recording of synaptic zinc in the brain by covalent chemistry-based semisynthetic biosensors.
4 affiliations
- 1Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
- 2Division of Synthetic Chemistry for Molecular Systems, SANKEN (The Institute of Scientific and Industrial Research), The University of Osaka, Ibaraki 567-0047, Japan.
- 3Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
- 4Biomolecular Organization Chemistry Research Section, Institute of Advanced Energy, Kyoto University, Uji 611-0011, Japan.
Abstract
Labile zinc ions (Zn²⁺) are stored in glutamatergic vesicles at specific excitatory synapses in the central nervous system and released into synaptic clefts in an activity-dependent manner. However, the precise roles of synaptic Zn²⁺ remain unclear due to a lack of tools capable of analyzing Zn²⁺ with synapse-level spatial resolution in vivo. Here, we developed neuroreceptor-based semisynthetic biosensors that function as integrating dosimeters, recording synaptic Zn²⁺ by covalent chemistry in the living mouse brain. Using a chemical knock-in strategy, we introduced activity-based Zn²⁺ probes with distinct affinities into endogenous α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or γ-aminobutyric acid type A receptors. These in-brain-constructed Zn²⁺ sensors enabled region-specific mapping of Zn²⁺ in synaptic clefts in the living mouse brain. Imaging-based analyses revealed differences in apparent Zn²⁺ levels at excitatory and inhibitory synapses across hippocampal regions during kainate-induced seizures, providing insights into the physiological and pathological functions of synaptic Zn²⁺.
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BibTeX
@article{zhu2026imaging,
title = {{Imaging and recording of synaptic zinc in the brain by covalent chemistry-based semisynthetic biosensors.}},
author = {Hao Zhu and Seiji Sakamotob and Keisuke Nakamura and Chengli Qiu and Kohei Nakajima and Hiroshi Nonaka and Itaru Hamachi},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2606947123},
url = {https://europepmc.org/article/MED/42863051},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Imaging and recording of synaptic zinc in the brain by covalent chemistry-based semisynthetic biosensors.
AU - Hao Zhu
AU - Seiji Sakamotob
AU - Keisuke Nakamura
AU - Chengli Qiu
AU - Kohei Nakajima
AU - Hiroshi Nonaka
AU - Itaru Hamachi
PY - 2026
DA - 2026/10/12
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2606947123
UR - https://europepmc.org/article/MED/42863051
AB - Labile zinc ions (Zn²⁺) are stored in glutamatergic vesicles at specific excitatory synapses in the central nervous system and released into synaptic clefts in an activity-dependent manner. However, the precise roles of synaptic Zn²⁺ remain unclear due to a lack of tools capable of analyzing Zn²⁺ with synapse-level spatial resolution in vivo. Here, we developed neuroreceptor-based semisynthetic biosensors that function as integrating dosimeters, recording synaptic Zn²⁺ by covalent chemistry in the living mouse brain. Using a chemical knock-in strategy, we introduced activity-based Zn²⁺ probes with distinct affinities into endogenous α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or γ-aminobutyric acid type A receptors. These in-brain-constructed Zn²⁺ sensors enabled region-specific mapping of Zn²⁺ in synaptic clefts in the living mouse brain. Imaging-based analyses revealed differences in apparent Zn²⁺ levels at excitatory and inhibitory synapses across hippocampal regions during kainate-induced seizures, providing insights into the physiological and pathological functions of synaptic Zn²⁺.
SN - 0027-8424
SN - 1091-6490
ER -