Focal adhesion kinase is a blood-testis barrier regulator
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/31604 https://dx.doi.org/10.1073/pnas.0813113106 |
Resumo: | In 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. |
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Siu, Erica RosannaWong, Elissa W. P.Mruk, Dolores D.Porto, Catarina Segreti [UNIFESP]Cheng, C. YanPopulat CouncilUniversidade Federal de São Paulo (UNIFESP)2016-01-24T13:52:38Z2016-01-24T13:52:38Z2009-06-09Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 106, n. 23, p. 9298-9303, 2009.0027-8424https://repositorio.unifesp.br/handle/11600/31604https://dx.doi.org/10.1073/pnas.081311310610.1073/pnas.0813113106WOS:000266817500036In 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.National Institute of Child Health and Human DevelopmentNational Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Populat Council, Ctr Biomed Res, New York, NY 10065 USAUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 São Paulo, BrazilNational Institute of Child Health and Human Development: R01 HD056034National Institute of Child Health and Human Development: R03 HD051512National Institute of Child Health and Human Development: U54 HD029990FAPESP: 06/51281-6Web of Science9298-9303engNatl Acad SciencesProceedings of the National Academy of Sciences of the United States of AmericaBasal ectoplasmic specializationCell-cell interactionSpermatogenesisTight junctionFocal adhesion kinase is a blood-testis barrier regulatorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/316042022-10-10 18:38:23.744metadata only accessoai:repositorio.unifesp.br:11600/31604Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-10-10T21:38:23Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Focal adhesion kinase is a blood-testis barrier regulator |
title |
Focal adhesion kinase is a blood-testis barrier regulator |
spellingShingle |
Focal adhesion kinase is a blood-testis barrier regulator Siu, Erica Rosanna Basal ectoplasmic specialization Cell-cell interaction Spermatogenesis Tight junction |
title_short |
Focal adhesion kinase is a blood-testis barrier regulator |
title_full |
Focal adhesion kinase is a blood-testis barrier regulator |
title_fullStr |
Focal adhesion kinase is a blood-testis barrier regulator |
title_full_unstemmed |
Focal adhesion kinase is a blood-testis barrier regulator |
title_sort |
Focal adhesion kinase is a blood-testis barrier regulator |
author |
Siu, Erica Rosanna |
author_facet |
Siu, Erica Rosanna Wong, Elissa W. P. Mruk, Dolores D. Porto, Catarina Segreti [UNIFESP] Cheng, C. Yan |
author_role |
author |
author2 |
Wong, Elissa W. P. Mruk, Dolores D. Porto, Catarina Segreti [UNIFESP] Cheng, C. Yan |
author2_role |
author author author author |
dc.contributor.institution.none.fl_str_mv |
Populat Council Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Siu, Erica Rosanna Wong, Elissa W. P. Mruk, Dolores D. Porto, Catarina Segreti [UNIFESP] Cheng, C. Yan |
dc.subject.eng.fl_str_mv |
Basal ectoplasmic specialization Cell-cell interaction Spermatogenesis Tight junction |
topic |
Basal ectoplasmic specialization Cell-cell interaction Spermatogenesis Tight junction |
description |
In 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. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-06-09 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:38Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Proceedings 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.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/31604 https://dx.doi.org/10.1073/pnas.0813113106 |
dc.identifier.issn.none.fl_str_mv |
0027-8424 |
dc.identifier.doi.none.fl_str_mv |
10.1073/pnas.0813113106 |
dc.identifier.wos.none.fl_str_mv |
WOS:000266817500036 |
identifier_str_mv |
Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 106, n. 23, p. 9298-9303, 2009. 0027-8424 10.1073/pnas.0813113106 WOS:000266817500036 |
url |
https://repositorio.unifesp.br/handle/11600/31604 https://dx.doi.org/10.1073/pnas.0813113106 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Proceedings of the National Academy of Sciences of the United States of America |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9298-9303 |
dc.publisher.none.fl_str_mv |
Natl Acad Sciences |
publisher.none.fl_str_mv |
Natl Acad Sciences |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
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1802764176142106624 |