内吞作用
跨细胞
内化
细胞生物学
内皮蛋白C受体
内体
动力素
受体介导的内吞作用
小窝
受体
化学
生物
细胞内
生物化学
信号转导
免疫学
凝血酶
血小板
作者
Ramesh C. Nayak,Prosenjit Sen,Samit Ghosh,Ramakrishnan Gopalakrishnan,Charles T. Esmon,Usha R. Pendurthi,L. Vijaya Mohan Rao
出处
期刊:Blood
[Elsevier BV]
日期:2009-08-27
卷期号:114 (9): 1974-1986
被引量:54
标识
DOI:10.1182/blood-2009-03-208900
摘要
Although the binding of endothelial cell protein C receptor (EPCR) to its ligands is well characterized at the biochemical level, it remains unclear how EPCR interaction with its ligands at the cell surface impacts its cellular trafficking. We characterized the cellular localization and trafficking of EPCR in endothelial cells and a heterologous expression system. Immunofluorescence confocal microscopy studies revealed that a majority of EPCR is localized on the cell surface in membrane microdomains that are positive for caveolin-1. A small fraction of EPCR is also localized intracellularly in the recycling compartment. Factor VIIa (FVIIa) or activated protein C binding to EPCR promoted the internalization of EPCR. EPCR and EPCR-bound ligands were endocytosed rapidly via a dynamin- and caveolar-dependent pathway. The endocytosed receptor-ligand complexes were accumulated in a recycling compartment before being targeted back to the cell surface. EPCR-mediated FVIIa endocytosis/recycling also resulted in transport of FVIIa from the apical to the basal side. In vivo studies in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early phase of FVIIa clearance. Overall, our results show that FVIIa or activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may facilitate the transcytosis of FVIIa and its clearance from the circulation.
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