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Article: Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics
Title | Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics |
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Authors | |
Keywords | Desmosome-like junction Seminiferous epithelial cycle Sertoli cell Spermatogenesis |
Issue Date | 2009 |
Publisher | National 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/179140 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Li, MWM | en_US |
dc.contributor.author | Mruk, DD | en_US |
dc.contributor.author | Lee, WM | en_US |
dc.contributor.author | Cheng, CY | en_US |
dc.date.accessioned | 2012-12-19T09:52:18Z | - |
dc.date.available | 2012-12-19T09:52:18Z | - |
dc.date.issued | 2009 | en_US |
dc.identifier.citation | Proceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 25, p. 10213-10218 | en_US |
dc.identifier.issn | 0027-8424 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/179140 | - |
dc.description.abstract | The 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.language | eng | en_US |
dc.publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org | en_US |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | en_US |
dc.subject | Desmosome-like junction | - |
dc.subject | Seminiferous epithelial cycle | - |
dc.subject | Sertoli cell | - |
dc.subject | Spermatogenesis | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Blood-Testis Barrier - Metabolism | en_US |
dc.subject.mesh | Cell Adhesion | en_US |
dc.subject.mesh | Connexin 43 - Genetics - Metabolism | en_US |
dc.subject.mesh | Gene Knockout Techniques | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Membrane Proteins - Metabolism | en_US |
dc.subject.mesh | Phosphoproteins - Metabolism | en_US |
dc.subject.mesh | Plakophilins - Genetics - Metabolism | en_US |
dc.subject.mesh | Rna Interference | en_US |
dc.subject.mesh | Rna, Small Interfering - Genetics | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.subject.mesh | Seminiferous Epithelium - Metabolism - Ultrastructure | en_US |
dc.subject.mesh | Sertoli Cells - Metabolism | en_US |
dc.subject.mesh | Spermatocytes - Metabolism | en_US |
dc.subject.mesh | Tight Junctions - Metabolism | en_US |
dc.title | Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lee, WM: hrszlwm@hku.hk | en_US |
dc.identifier.authority | Lee, WM=rp00728 | en_US |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.1073/pnas.0901700106 | en_US |
dc.identifier.pmid | 19509333 | - |
dc.identifier.pmcid | PMC2700929 | - |
dc.identifier.scopus | eid_2-s2.0-67649834031 | en_US |
dc.identifier.hkuros | 164873 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-67649834031&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 106 | en_US |
dc.identifier.issue | 25 | en_US |
dc.identifier.spage | 10213 | en_US |
dc.identifier.epage | 10218 | en_US |
dc.identifier.isi | WOS:000267292200028 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Li, MWM=27168276300 | en_US |
dc.identifier.scopusauthorid | Mruk, DD=6701823934 | en_US |
dc.identifier.scopusauthorid | Lee, WM=24799156600 | en_US |
dc.identifier.scopusauthorid | Cheng, CY=7404797787 | en_US |
dc.identifier.issnl | 0027-8424 | - |