Cell-Specific Optical Control of AMPA Glutamate Receptors with a Photoswitchable Tethered Antagonist

被引：1

作者：

Leippe, Philipp ^{[1
]}

Donthamsetti, Prashant ^{[2
]}

Ko, Tongil ^{[3
]}

Stanley, Cherise ^{[4
,5
,6
]}

Isacoff, Ehud ^{[4
,5
,6
]}

Trauner, Dirk ^{[3
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[2] Vanderbilt Univ, Dept Pharmacol, 2220 Pierce Ave,Preston Res Bldg 460, Nashville, TN 37232 USA

[3] Univ Penn, Sch Arts & Sci, Dept Chem, Dept Syst Pharmacol & Translat Therapeut, 231 South 34th St, Philadelphia, PA 19104 USA

[4] Univ Calif Berkeley, Dept Neurosci, 271 Weill Hall MC 3220, Berkeley, CA 94720 USA

[5] Univ Calif Berkeley, Dept Mol & Cell Biol, 271 Weill Hall MC 3220, Berkeley, CA 94720 USA

[6] Univ Calif Berkeley, Helen Wills Neurosci Inst, 271 Weill Hall MC 3220, Berkeley, CA 94720 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2024年 / 63卷 / 49期

基金：

美国国家卫生研究院;

关键词：

Photopharmacology; Bioconjugation; AMPA Receptor; Synaptic Transmission; Neuroscience;

D O I：

10.1002/anie.202411181

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

AMPA receptors (AMPARs) are the main drivers of excitatory glutamatergic transmission in the brain, central to synaptic plasticity, and are key drug targets. However, AMPARs are expressed in virtually every neuron in the central nervous system and are activated with complex temporal dynamics, making it difficult to determine their functional roles with sufficient precision. Here we describe a cell specific, light-controllable competitive antagonist for the AMPA receptor called MP-GluAblock that combines the temporal precision of a photo-switchable ligand with the spatial and cellular specificity of a genetically-encoded membrane-anchor protein. This tool could pave the way for controlling endogenous AMPARs in neural circuits with cellular, spatial, and temporal specificity.

引用

页数：5

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