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Article: Connexin 43 is critical to maintain the homeostasis of the blood-testis barrier via its effects on tight junction reassembly

TitleConnexin 43 is critical to maintain the homeostasis of the blood-testis barrier via its effects on tight junction reassembly
Authors
KeywordsBisphenol A
Calcium switch
Gap junction
Seminiferous epithelial cycle
Spermatogenesis
Issue Date2010
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 42, p. 17998-18003 How to Cite?
AbstractIn mammalian testes, the blood-testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted by coexisting tight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood-tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the "resealing" of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/140892
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of Health [National Institute of Child Health and Human Development]R01 HD056034
U54 HD029990
Hong Kong Research Grants CouncilHKU7693/07M
Funding Information:

We thank Dr. Alison North (The Rockefeller University Bio-Imaging Resource Center) for technical support in the FRAP study. This work was supported in part by grants from the National Institutes of Health [National Institute of Child Health and Human Development, Grants R01 HD056034 (to C.Y.C.) and U54 HD029990 Project 5 (to C.Y.C.)]; and Hong Kong Research Grants Council, Grant HKU7693/07M (to W.M.L.).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, MWMen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2011-09-23T06:21:00Z-
dc.date.available2011-09-23T06:21:00Z-
dc.date.issued2010en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 42, p. 17998-18003en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/140892-
dc.description.abstractIn mammalian testes, the blood-testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted by coexisting tight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood-tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the "resealing" of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectBisphenol Aen_HK
dc.subjectCalcium switchen_HK
dc.subjectGap junctionen_HK
dc.subjectSeminiferous epithelial cycleen_HK
dc.subjectSpermatogenesisen_HK
dc.subject.meshBlood-Testis Barrier-
dc.subject.meshConnexin 43 - physiology-
dc.subject.meshHomeostasis - physiology-
dc.subject.meshPhenols - pharmacology-
dc.subject.meshTight Junctions-
dc.titleConnexin 43 is critical to maintain the homeostasis of the blood-testis barrier via its effects on tight junction reassemblyen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1007047107en_HK
dc.identifier.pmid20921394-
dc.identifier.pmcidPMC2964254-
dc.identifier.scopuseid_2-s2.0-78149242584en_HK
dc.identifier.hkuros194363en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78149242584&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume107en_HK
dc.identifier.issue42en_HK
dc.identifier.spage17998en_HK
dc.identifier.epage18003en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000283184800030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, MWM=35337441200en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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