ArticleProceedings of the National Academy of Sciences of the United States of America2011
P-glycoprotein regulates blood-testis barrier dynamics via its effects on the occludin/zonula occludens 1 (ZO-1) protein complex mediated by focal adhesion kinase (FAK).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Diurnal testosterone oscillations gate drug delivery via phase separation of ZO-1 at the blood-testis barrier in mice.Communications biology · 2026Article
- Comparative Analysis of Testicular Transcriptional and Translational Landscapes in Yak and Cattle-Yak: Implications for Hybrid Male Sterility.Biomolecules · 2025Article
- Plant-Based Products Originating from Serbia That Affect P-glycoprotein Activity.Molecules (Basel, Switzerland) · 2024Review
- MARK2 and MARK4 Regulate Sertoli Cell BTB Dynamics Through Microtubule and Actin Cytoskeletons.Endocrinology · 2022Article
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Drug transport across the blood-testis barrier.American journal of translational research · 2022Review
- Effect of Nano-Titanium Dioxide on Blood-Testis Barrier and MAPK Signaling Pathway in Male Mice.Biological trace element research · 2021Article
- Disruption of anchoring junctions in the testes of experimental varicocele rats.Experimental and therapeutic medicine · 2021Article
- The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways.International journal of molecular sciences · 2021Article
- CRISPR/Cas9 mutagenesis reveals a role for ABCB1 in gut immune responses to Vibrio diazotrophicus in sea urchin larvae.The Journal of experimental biology · 2021Article
- Identification of abnormal protein expressions associated with mouse spermatogenesis induced by cyclophosphamide.Journal of cellular and molecular medicine · 2021Article
- F5-Peptide and mTORC1/rpS6 Effectively Enhance BTB Transport Function in the Testis-Lesson From the Adjudin Model.Endocrinology · 2019Article
- JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling.Cell death & disease · 2018Article
- Signaling pathways regulating blood-tissue barriers - Lesson from the testis.Biochimica et biophysica acta. Biomembranes · 2018Review
- Abcb1a and Abcb1b genes function differentially in blood-testis barrier dynamics in the rat.Cell death & disease · 2017Article
- Disruption of outer blood-retinal barrier by Toxoplasma gondii-infected monocytes is mediated by paracrinely activated FAK signaling.PloS one · 2017Article
- Rack1 Mediates the Interaction of P-Glycoprotein with Anxa2 and Regulates Migration and Invasion of Multidrug-Resistant Breast Cancer Cells.International journal of molecular sciences · 2016Article
- Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway.Scientific reports · 2016Article
- Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) - Lesson from Adjudin.Current medicinal chemistry · 2016Review
- Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology.World journal of gastroenterology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The blood-testis barrier (BTB), one of the tightest blood-tissue barriers in the mammalian body, creates an immune-privileged site for postmeiotic spermatid development to avoid the production of antibodies against spermatid-specific antigens, many of which express transiently during spermiogenesis and spermiation. However, the BTB undergoes extensive restructuring at stage VIII of the epithelial cycle to facilitate the transit of preleptotene spermatocytes and to prepare for meiosis. This action thus prompted us to investigate whether this stage can be a physiological window for the delivery of therapeutic and/or contraceptive drugs across the BTB to exert their effects at the immune-privileged site. Herein, we report findings that P-glycoprotein, an ATP-dependent efflux drug transporter and an integrated component of the occludin/zonula occludens 1 (ZO-1) adhesion complex at the BTB, structurally interacted with focal adhesion kinase (FAK), creating the occludin/ZO-1/FAK/P-glycoprotein regulatory complex. Interestingly, a knockdown of P-glycoprotein by RNAi was found to impede Sertoli cell BTB function, making the tight junction (TJ) barrier "leaky." This effect was mediated by changes in the protein phosphorylation status of occludin via the action of FAK, thereby affecting the endocytic vesicle-mediated protein trafficking events that destabilized the TJ barrier. However, the silencing of P-glycoprotein, although capable of impeding drug transport across the BTB and TJ permeability barrier function, was not able to induce the BTB to be "freely" permeable to adjudin. These findings indicate that P-glycoprotein is involved in BTB restructuring during spermatogenesis but that P-glycoprotein-mediated restructuring does not "open up" the BTB to make it freely permeable to drugs.
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Registered trials
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.