RGD Reference Report - 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). - Rat Genome Database

RGD Reference Report - 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). - Rat Genome Database

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General

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).
Authors:	Su, Linlin Mruk, Dolores D Lui, Wing-Yee Lee, Will M Cheng, C Yan
Citation:	Su L, etal., Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19623-8. doi: 10.1073/pnas.1111414108. Epub 2011 Nov 21.
RGD ID:	13432329
Pubmed:	PMID:22106313 (View Abstract at PubMed)
PMCID:	PMC3241815 (View Article at PubMed Central)
DOI:	DOI:10.1073/pnas.1111414108 (Journal Full-text)
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.

Gene Ontology Annotations Click to see Annotation Detail View

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
protein binding	enables	IPI	UniProtKB:F1M4A0	13432329	PMID:22106313	IntAct
protein binding	enables	IPI	UniProtKB:O35346	13432329	PMID:22106313	IntAct
protein binding	enables	IPI	UniProtKB:Q6P6T5	13432329; 13432329	PMID:22106313	IntAct

Objects Annotated

Genes (Rattus norvegicus)

Ocln (occludin)

Ptk2 (protein tyrosine kinase 2)

Tjp1 (tight junction protein 1)

Additional Information