Steichen Hailey, Xue Jianxiang, Zaidman Nathan A
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States.
Am J Physiol Renal Physiol. 2025 Jul 1;329(1):F11-F19. doi: 10.1152/ajprenal.00134.2025. Epub 2025 May 15.
Adhesion G protein-coupled receptors (AGPCRs) are a class of seven-transmembrane receptors that sense cell-to-cell and cell-to-extracellular matrix transient adhesive events. AGPCRs are physiologically relevant and regulate processes throughout the body. However, the physiological roles of many AGPCRs are undefined. Unlike G protein-coupled receptors (GPCRs) that bind soluble agonists, AGPCRs uniquely depend on extracellular interactions and stimuli to facilitate endogenous activation by a tethered peptide agonist. Therefore, it is paramount to determine the cellular localization of AGPCRs to begin unraveling their functional roles. In the present work, we have identified the most abundant AGPCRs expressed in the murine kidney and determined their cellular localization through a combination of single-nucleus RNA sequencing and RNAscope fluorescent in situ hybridization. We not only report the transcriptional abundance of six AGPCRs that are expressed in a cell-specific manner but also demonstrate that , a receptor with low but specific abundance by snRNAseq, is detected in a subset of principal cells by RNAscope. In addition, we identify cell-specific transcript variants of in the kidney, supporting a significant role of alternative splicing in AGPCR physiology. These data will assist in the generation of tissue- and cell-specific hypotheses and enable future investigations into the physiological roles of AGPCRs in the kidney and other tissues. Adhesion G protein-coupled receptors (GPCRs) are a unique class of receptors that regulate numerous physiological processes throughout the body. Here, we identify and localize the AGPCRs expressed in the mouse kidney using a multimodal approach. This work will provide a foundation for future investigations into the novel physiological roles of AGPCRs in the kidney.
黏附G蛋白偶联受体（AGPCRs）是一类七跨膜受体，可感知细胞间以及细胞与细胞外基质之间的瞬时黏附事件。AGPCRs具有生理相关性，并调节全身各处的生理过程。然而，许多AGPCRs的生理作用尚不清楚。与结合可溶性激动剂的G蛋白偶联受体（GPCRs）不同，AGPCRs独特地依赖于细胞外相互作用和刺激，以促进由拴系肽激动剂介导的内源性激活。因此，确定AGPCRs的细胞定位对于开始揭示其功能作用至关重要。在本研究中，我们鉴定了小鼠肾脏中表达最丰富的AGPCRs，并通过单核RNA测序和RNAscope荧光原位杂交相结合的方法确定了它们的细胞定位。我们不仅报告了以细胞特异性方式表达的六种AGPCRs的转录丰度，还证明了通过RNAscope在一部分主细胞中检测到了一种在单细胞核RNA测序中丰度较低但具有特异性的受体。此外，我们在肾脏中鉴定了 的细胞特异性转录变体，支持可变剪接在AGPCR生理过程中的重要作用。这些数据将有助于生成组织和细胞特异性的假设，并为未来研究AGPCRs在肾脏和其他组织中的生理作用提供支持。黏附G蛋白偶联受体（GPCRs）是一类独特的受体，可调节全身众多生理过程。在这里，我们使用多模态方法鉴定并定位了小鼠肾脏中表达的AGPCRs。这项工作将为未来研究AGPCRs在肾脏中的新生理作用奠定基础。
