ArticleThe Journal of biological chemistry2016
Recycling and Endosomal Sorting of Protease-activated Receptor-1 Is Distinctly Regulated by Rab11A and Rab11B Proteins.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment.EMBO molecular medicine · 2026Article
- Rab11Bis required for binding and entry of recent H3N2, but not H1N1, influenza A isolates.Journal of virology · 2026Article
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- Rab11B is required for binding and entry of recent H3N2, but not H1N1, influenza A isolates.bioRxiv : the preprint server for biology · 2025Article
- Targeting F2R/PAR1 with ligand decorated lipid nanocarriers for enhanced drug delivery into ovarian cancer cells.Frontiers in drug delivery · 2025Article
- Rab11b is necessary for mitochondrial integrity and function in gut epithelial cells.Frontiers in cell and developmental biology · 2025Article
- Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.Cancers · 2024Review
- Revealing potential Rab proteins participate in regulation of secretory autophagy machinery.The Kaohsiung journal of medical sciences · 2024Article
- Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.Heliyon · 2024Article
- Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.Cell research · 2023Article
- TRAP-induced PAR1 expression with its mechanism during AMI in a rat model.BMC cardiovascular disorders · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Host Cell Signatures of the Envelopment Site within Beta-Herpes Virions.International journal of molecular sciences · 2022Review
- Vascular Endothelial Cells Produce Coagulation Factors That Control Their Growth via Joint Protease-Activated Receptor and C5a Receptor 1 (CD88) Signaling.The American journal of pathology · 2022Article
- Rab GTPases: The principal players in crafting the regulatory landscape of endosomal trafficking.Computational and structural biotechnology journal · 2022Review
- Protease Activated Receptors and Arthritis.International journal of molecular sciences · 2021Review
- Review
- Hidden proteome of synaptic vesicles in the mammalian brain.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis.Frontiers in oncology · 2020Review
- Expression analysis of Rab11 during zebrafish embryonic development.BMC developmental biology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that undergoes proteolytic irreversible activation by coagulant and anti-coagulant proteases. Given the irreversible activation of PAR1, signaling by the receptor is tightly regulated through desensitization and intracellular trafficking. PAR1 displays both constitutive and agonist-induced internalization. Constitutive internalization of PAR1 is important for generating an internal pool of naïve receptors that replenish the cell surface and facilitate resensitization, whereas agonist-induced internalization of PAR1 is critical for terminating G protein signaling. We showed that PAR1 constitutive internalization is mediated by the adaptor protein complex-2 (AP-2), whereas AP-2 and epsin control agonist-induced PAR1 internalization. However, the mechanisms that regulate PAR1 recycling are not known. In the present study we screened a siRNA library of 140 different membrane trafficking proteins to identify key regulators of PAR1 intracellular trafficking. In addition to known mediators of PAR1 endocytosis, we identified Rab11B as a critical regulator of PAR1 trafficking. We found that siRNA-mediated depletion of Rab11B and not Rab11A blocks PAR1 recycling, which enhanced receptor lysosomal degradation. Although Rab11A is not required for PAR1 recycling, depletion of Rab11A resulted in intracellular accumulation of PAR1 through disruption of basal lysosomal degradation of the receptor. Moreover, enhanced degradation of PAR1 observed in Rab11B-deficient cells is blocked by depletion of Rab11A and the autophagy related-5 protein, suggesting that PAR1 is shuttled to an autophagic degradation pathway in the absence of Rab11B recycling. Together these findings suggest that Rab11A and Rab11B differentially regulate intracellular trafficking of PAR1 through distinct endosomal sorting mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.