Wang Lianqing,Lan Yongting,Du Yanqin,Xiang Xinxin,Tian Wenxiu,Yang Baoye,Li Tao,Zhai Qiaoli
Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation. However, the bone-related function of plastin 1, another family member of plastins, has not been assessed. In this study, we addressed the functional importance of plastin 1 in osteoblasts. We characterized the expression patterns of plastin 1 during osteoblast differentiation and revealed its important role in this process. In both HEK 293T and hFOB1.19 cells, plastin 1 was demonstrated to regulate intracellular Ca2+. Accordingly, we revealed that higher Ca2+ concentration promotes osteoblast differentiation. Finally, we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency. Together, our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+. Our work sheds new light on the role played by plastins in bone homeostasis.
Liangxia Wang,Weijian Zhao,Wenmei Zhang,Tian Chen,Mengying Wang,Xianbin Meng,Guangsheng Guo,Xiayan Wang
As a selective permeability interface, the Blood-Brain Barrier (BBB) restricts drug access to the brain, complicating theranostic strategies for neurological disorders. The selective permeability of the blood-brain barrier is primarily controlled by brain microvascular endothelial cells (BMECs). Cell surface proteins can be endocytosed into brain microvascular endothelial cells, serving as promising candidates for receptor-mediated transcytosis across the blood-brain barrier. However, to date, systematic analysis of the internalization of surface proteins in human blood-brain barrier models still has some limitations. In this study, we employed high-resolution mass spectrometry (HRMS) based on Data-Independent Acquisition (DIA) combined with cell surface biotinylation to comprehensively identify internalized surface proteins in human brain microvascular endothelial cells (HBEC-5i). This approach overcomes traditional proteomics limitations, enabling high-throughput quantification of hundreds of surface proteins. Our analysis identified 232 internalized cell-surface proteins, with 54 showing HBEC-5i specificity compared to dermal (HMEC-1) and pulmonary (HULEC-5a) microvascular endothelial cells. Through integration with mRNA expression data from public databases and immunohistochemical evidence from the Human Protein Atlas, we identified Plastin 3 (PLS3) and Collectin Subfamily Member 12 (COLEC12) as key candidate proteins. Both proteins exhibited elevated expression and distinct plasma membrane localization patterns in HBEC-5i cells. Our study highlights the unique advantages of DIA high-resolution mass spectrometry in profiling BBB-related proteins and provides valuable insights for developing targeted strategies to enhance central nervous system drug delivery.
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