Expanded LUXendin Color Palette for GLP1R Detection and Visualization In Vitro and In Vivo.
Expanded LUXendin Color Palette for GLP1R Detection and Visualization In Vitro and In Vivo.
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DOI：
10.1021/jacsau.2c00130
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发表时间：
2022-04-25
期刊：
影响因子：
8
通讯作者：
Broichhagen, Johannes
中科院分区：
文献类型：
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作者：
Ast, Julia;Novak, Alissa N;Podewin, Tom;Fine, Nicholas H F;Jones, Ben;Tomas, Alejandra;Birke, Ramona;RoSSmann, Kilian;Mathes, Bettina;Eichhorst, Jenny;Lehmann, Martin;Linnemann, Amelia K;Hodson, David J;Broichhagen, Johannes
胰高血糖素样肽-1受体（GLP 1 R）在外周组织和脑中表达，在脑中对代谢和炎症过程发挥多效性作用。GLP 1 R的检测和可视化仍然具有挑战性，部分原因是缺乏经过验证的试剂。以前，我们产生了LUXendins，拮抗性红色和远红荧光探针，用于在活细胞和固定细胞/组织中特异性标记GLP 1 R。我们现在通过合成和测试LUXendin 492、LUXendin 551、LUXendin 615和LUXendin 762，将此概念扩展到绿色和近红外颜色范围。所有四种探针都明亮且特异性地标记细胞和胰岛中的GLP 1 R。此外，LUXendin 551在临床前啮齿动物模型中充当化学β细胞报告基因，而LUXendin 762允许非侵入性成像，突出显示差异可及的GLP 1 R群体。因此，我们将LUXendins的调色板扩展到七种不同的光谱，通过超分辨率成像和整个动物成像，在大多数实验室中使用宽视场显微镜进行了一系列实验。有了这个，我们预计LUXendins将继续产生新的和具体的见解GLP 1 R生物学。
The glucagon-like peptide-1 receptor (GLP1R) is expressed in peripheral tissues and the brain, where it exerts pleiotropic actions on metabolic and inflammatory processes. Detection and visualization of GLP1R remains challenging, partly due to a lack of validated reagents. Previously, we generated LUXendins, antagonistic red and far-red fluorescent probes for specific labeling of GLP1R in live and fixed cells/tissues. We now extend this concept to the green and near-infrared color ranges by synthesizing and testing LUXendin492, LUXendin551, LUXendin615, and LUXendin762. All four probes brightly and specifically label GLP1R in cells and pancreatic islets. Further, LUXendin551 acts as a chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows noninvasive imaging, highlighting differentially accessible GLP1R populations. We thus expand the color palette of LUXendins to seven different spectra, opening up a range of experiments using wide-field microscopy available in most labs through super-resolution imaging and whole animal imaging. With this, we expect that LUXendins will continue to generate novel and specific insights into GLP1R biology.