Focal adhesion kinase is a blood-testis barrier regulator

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dc.contributor.authorSiu, Erica Rosanna
dc.contributor.authorWong, Elissa W. P.
dc.contributor.authorMruk, Dolores D.
dc.contributor.authorPorto, Catarina Segreti [UNIFESP]
dc.contributor.authorCheng, C. Yan
dc.contributor.institutionPopulat Council
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:52:38Z
dc.date.available2016-01-24T13:52:38Z
dc.date.issued2009-06-09
dc.description.abstractIn mammalian testes, such as rats, the mechanism(s) that regulate blood-testis barrier (BTB) restructuring at stages VIII-IX of the seminiferous epithelial cycle of spermatogenesis to facilitate the transit of preleptotene/leptotene spermatocytes is not known. This is due to the lack of information on the regulatory proteins at the BTB. Herein, focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, is shown to structurally interact with occludin and ZO-1 to form a functional protein complex at the BTB. Its expression at the BTB in the seminiferous epithelium is stage specific, being lowest at stage VIII-IX tubules, analogous to the expression pattern of occludin. Using primary Sertoli cells cultured in vitro with an established tight junction (TJ) permeability barrier that mimics the BTB in vivo, the knockdown of FAK by RNAi led to a transient disruption of the TJ barrier. This was accompanied by a loss of association between occludin and ZO-1, likely the result of reduced occludin phosphorylation at Tyr and Ser residues, but not Thr, which in turn led to a redistribution of occludin at the Sertoli-Sertoli cell interface, moving from cell membrane into cell cytosol, thereby disrupting the BTB. These findings suggest that a similar mechanism is in place in the testis in vivo to regulate BTB restructuring to facilitate the transit of primary spermatocytes. Furthermore, FAK was shown to be a molecular target of cadmium because its knockdown would desensitize Sertoli cells to cadmium-induced TJ barrier disruption. in summary, FAK is a unique regulator of BTB dynamics in the testis.en
dc.description.affiliationPopulat Council, Ctr Biomed Res, New York, NY 10065 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institute of Child Health and Human Development
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipIDNational Institute of Child Health and Human Development: R01 HD056034
dc.description.sponsorshipIDNational Institute of Child Health and Human Development: R03 HD051512
dc.description.sponsorshipIDNational Institute of Child Health and Human Development: U54 HD029990
dc.description.sponsorshipIDFAPESP: 06/51281-6pt
dc.format.extent9298-9303
dc.identifierhttps://dx.doi.org/10.1073/pnas.0813113106
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 106, n. 23, p. 9298-9303, 2009.
dc.identifier.doi10.1073/pnas.0813113106
dc.identifier.issn0027-8424
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/31604
dc.identifier.wosWOS:000266817500036
dc.language.isoeng
dc.publisherNatl Acad Sciences
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBasal ectoplasmic specializationen
dc.subjectCell-cell interactionen
dc.subjectSpermatogenesisen
dc.subjectTight junctionen
dc.titleFocal adhesion kinase is a blood-testis barrier regulatoren
dc.typeinfo:eu-repo/semantics/article
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