Zijian Zhu, Zuzhi Jiang, Yupu Wang, Khanh Hung Nguyen, Yuxiang Zhang, Cameron Genxuan Lian, D.R. Mani, Jun Zheng, Lang Ding, Shihong Max Gao, Ruyue Alps Xia, Anne Kuszpit, Sarah Lindo, Crystall Lopez, Catherine Lindsey, Brooke Groff, Xinhong Chen, Jiahui Wu, Weiliang Xia, Wei Li, Xiaorong Liu, Viviana Gradinaru, Steven A. Carr, Namrata D. Udeshi, Jiefu Li
At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal surface in vivo, broadly applicable to any vertebrate. Quantitative mass spectrometry revealed the luminal surface proteome of the mouse brain vasculature and its temporal evolution from development to aging. In vivo genetic perturbation found that the arginine transporter SLC7A1 and the nitric oxide synthase NOS3 are needed for blood-brain barrier integrity in neonatal but not adult mice, whereas the hyaluronan degradation enzyme HYAL2 safeguards the barrier throughout the lifespan. By characterizing the proteomic dynamics of the vasculature luminal surface, the study links the metabolism of nitric oxide and hyaluronan to blood-brain barrier integrity.