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Article: Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics

TitleConnexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics
Authors
Issue Date2009
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, 2009, v. 106 n. 25, p. 10213-10218 How to Cite?
AbstractThe blood-testis barrier (BTB) formed by adjacent Sertoli cells is composed of coexisting tight junction (TJ), basal ectoplasmic specialization (ES), and desmosome-like junction. Desmosome-like junctions display structural features of desmosome and gap junctions, but its function at the BTB remains unknown. Herein, we demonstrate that connexin 43 (Cx43), a gap junction integral membrane protein, structurally interacts with desmosomal protein plakophilin-2 (PKP2), basal ES proteins N-cadherin and β-catenin, and signaling molecule c-Src, but not with the TJ proteins occludin and ZO-1 in the seminiferous epithelium of adult rats. The localization of Cx43 in the seminiferous epithelium during (i) the normal epithelial cycle of spermatogenesis and (ii) anchoring junction restructuring at the Sertoli-spermatid interface induced by adjudin which mimics junction restructuring events during spermatogenesis have suggested that Cx43 is involved in cell adhesion. The knockdown of Cx43 by RNAi technique using specific siRNA duplexes was performed in primary Sertoli cell cultures with an established TJ permeability barrier that mimicked the BTB in vivo. This knockdown of Cx43 affected neither the TJ barrier function nor the steady-state levels of junction proteins of TJ, basal ES, and desmosome-like junction. However, after the knockdown of both Cx43 and PKP2, the Sertoli cell TJ barrier function was perturbed transiently. This perturbation was concomitant with a mislocalization of occludin and ZO-1 from the cell-cell interface. In summary, Cx43 and PKP2 form a protein complex within the desmosome-like junction to regulate cell adhesion at the BTB, partly through its effects on the occludin/ZO-1 complex, so as to facilitate the transit of primary preleptotene spermatocytes.
Persistent Identifierhttp://hdl.handle.net/10722/179140
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, MWMen_US
dc.contributor.authorMruk, DDen_US
dc.contributor.authorLee, WMen_US
dc.contributor.authorCheng, CYen_US
dc.date.accessioned2012-12-19T09:52:18Z-
dc.date.available2012-12-19T09:52:18Z-
dc.date.issued2009en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 25, p. 10213-10218en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/179140-
dc.description.abstractThe blood-testis barrier (BTB) formed by adjacent Sertoli cells is composed of coexisting tight junction (TJ), basal ectoplasmic specialization (ES), and desmosome-like junction. Desmosome-like junctions display structural features of desmosome and gap junctions, but its function at the BTB remains unknown. Herein, we demonstrate that connexin 43 (Cx43), a gap junction integral membrane protein, structurally interacts with desmosomal protein plakophilin-2 (PKP2), basal ES proteins N-cadherin and β-catenin, and signaling molecule c-Src, but not with the TJ proteins occludin and ZO-1 in the seminiferous epithelium of adult rats. The localization of Cx43 in the seminiferous epithelium during (i) the normal epithelial cycle of spermatogenesis and (ii) anchoring junction restructuring at the Sertoli-spermatid interface induced by adjudin which mimics junction restructuring events during spermatogenesis have suggested that Cx43 is involved in cell adhesion. The knockdown of Cx43 by RNAi technique using specific siRNA duplexes was performed in primary Sertoli cell cultures with an established TJ permeability barrier that mimicked the BTB in vivo. This knockdown of Cx43 affected neither the TJ barrier function nor the steady-state levels of junction proteins of TJ, basal ES, and desmosome-like junction. However, after the knockdown of both Cx43 and PKP2, the Sertoli cell TJ barrier function was perturbed transiently. This perturbation was concomitant with a mislocalization of occludin and ZO-1 from the cell-cell interface. In summary, Cx43 and PKP2 form a protein complex within the desmosome-like junction to regulate cell adhesion at the BTB, partly through its effects on the occludin/ZO-1 complex, so as to facilitate the transit of primary preleptotene spermatocytes.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlood-Testis Barrier - Metabolismen_US
dc.subject.meshCell Adhesionen_US
dc.subject.meshConnexin 43 - Genetics - Metabolismen_US
dc.subject.meshGene Knockout Techniquesen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Proteins - Metabolismen_US
dc.subject.meshPhosphoproteins - Metabolismen_US
dc.subject.meshPlakophilins - Genetics - Metabolismen_US
dc.subject.meshRna Interferenceen_US
dc.subject.meshRna, Small Interfering - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshSeminiferous Epithelium - Metabolism - Ultrastructureen_US
dc.subject.meshSertoli Cells - Metabolismen_US
dc.subject.meshSpermatocytes - Metabolismen_US
dc.subject.meshTight Junctions - Metabolismen_US
dc.titleConnexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamicsen_US
dc.typeArticleen_US
dc.identifier.emailLee, WM: hrszlwm@hku.hken_US
dc.identifier.authorityLee, WM=rp00728en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1073/pnas.0901700106en_US
dc.identifier.pmid19509333-
dc.identifier.pmcidPMC2700929-
dc.identifier.scopuseid_2-s2.0-67649834031en_US
dc.identifier.hkuros164873-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649834031&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume106en_US
dc.identifier.issue25en_US
dc.identifier.spage10213en_US
dc.identifier.epage10218en_US
dc.identifier.isiWOS:000267292200028-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, MWM=27168276300en_US
dc.identifier.scopusauthoridMruk, DD=6701823934en_US
dc.identifier.scopusauthoridLee, WM=24799156600en_US
dc.identifier.scopusauthoridCheng, CY=7404797787en_US

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