Cho Youngjoon, Jeong Inyoung, Kim Kwang-Eun, Rhee Hyun-Woo
Department of Chemistry, Seoul National University, Seoul 08826, Korea.
Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
ACS Chem Biol. 2025 Jan 17;20(1):86-93. doi: 10.1021/acschembio.4c00419. Epub 2024 Dec 18.
Cell-cell interactions are fundamental in biology for maintaining physiological conditions with direct contact being the most straightforward mode of interaction. Recent advancements have led to the development of various chemical tools for detecting or identifying these interactions. However, the use of exogenous cues, such as toxic reagents, bulky probes, and light irradiation, can disrupt normal cell physiology. For example, the toxicity of hydrogen peroxide (HO) limits the applications of peroxidases in the proximity labeling field. In this study, we aimed to address this limitation by demonstrating that membrane-localized horseradish peroxidase (HRP-TM) efficiently utilizes endogenously generated extracellular HO. By harnessing endogenous HO, we observed that HRP-TM-expressing cells can effectively label contacting cells without the need for exogenous HO treatment. Furthermore, we confirmed that HRP-TM labels proximal cells in an interaction-dependent manner. These findings offer a novel approach for studying cell-cell interactions under more physiological conditions without the confounding effects of exogenous stimuli. Our study contributes to elucidating cell-cell interaction networks in various model organisms, providing valuable insights into the dynamic interplay between cells in their native network.
细胞间相互作用在生物学中对于维持生理状态至关重要，直接接触是最直接的相互作用方式。最近的进展促使了各种用于检测或识别这些相互作用的化学工具的开发。然而，使用外源性线索，如有毒试剂、大型探针和光照射，可能会破坏正常细胞生理。例如，过氧化氢（HO）的毒性限制了过氧化物酶在邻近标记领域的应用。在本研究中，我们旨在通过证明膜定位辣根过氧化物酶（HRP-TM）有效利用内源性产生的细胞外HO来解决这一限制。通过利用内源性HO，我们观察到表达HRP-TM的细胞可以有效地标记接触细胞，而无需外源性HO处理。此外，我们证实HRP-TM以相互作用依赖的方式标记近端细胞。这些发现为在更生理条件下研究细胞间相互作用提供了一种新方法，而不会受到外源性刺激的混杂影响。我们的研究有助于阐明各种模式生物中的细胞间相互作用网络，为细胞在其天然网络中的动态相互作用提供有价值的见解。
