Surfaceome Profiling Identifies Basigin-Chaperoned Protein Clients.
Surfaceome Profiling Identifies Basigin-Chaperoned Protein Clients.
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表面组分析可识别 Basigin 陪伴的蛋白质客户。
DOI：
10.1002/cbic.202300073
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Huang,MiaL
中科院分区：
文献类型：
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作者：
Vilen,Zak;Joeh,Eugene;Lee,Elizabeth;Huang,MiaL
表面蛋白质组或“表面组”是细胞生物学的关键介质，促进细胞与细胞之间的相互作用和与细胞外生物分子的通信。表面组的成分可以作为改变细胞状态的生物标志物和作为药物干预的靶点。虽然细胞表面运输的一些途径被很好地表征以允许预测表面定位，但一些非典型运输机制没有。Basigin（Bsg）是一种细胞表面糖蛋白，已被证明可以陪伴蛋白质客户到细胞表面。然而，了解哪些蛋白质是由Bsg提供的并不总是那么简单。为了加速这种鉴定，我们应用了一种表面组邻近标记方法，该方法与基于定量质谱的蛋白质组学相结合，以识别肝星状细胞表面组中响应Bsg遗传丢失而发生的变化。使用这种策略，我们观察到Bsg的丢失导致单羧酸转运蛋白MCT1和MCT4的细胞表面表达相应减少。我们还发现，这些关系是BSG所独有的，而在相关家族成员神经质蛋白（Nptn）中没有发现。这些结果建立了利用表面组邻近标记方法来确定细胞表面伴侣蛋白的客户。
The surface proteome or “surfaceome” is a critical mediator of cellular biology, facilitating cell‐to‐cell interactions and communication with extracellular biomolecules. Constituents of the surfaceome can serve as biomarkers for changing cell states and as targets for pharmacological intervention. While some pathways of cell surface trafficking are well characterized to allow prediction of surface localization, some non‐canonical trafficking mechanisms do not. Basigin (Bsg), a cell surface glycoprotein, has been shown to chaperone protein clients to the cell surface. However, understanding which proteins are served by Bsg is not always straightforward. To accelerate such identification, we applied a surfaceome proximity labeling method that is integrated with quantitative mass spectrometry‐based proteomics to discern changes in the surfaceome of hepatic stellate cells that occur in response to the genetic loss of Bsg. Using this strategy, we observed that the loss of Bsg leads to corresponding reductions in the cell surface expression of monocarboxylate transporters MCT1 and MCT4. We also found that these relationships were unique to Bsg and not found in neuroplastin (Nptn), a related family member. These results establish the utility of the surfaceome proximity labeling method to determine clients of cell surface chaperone proteins.