Interfering amino terminal peptides and functional implications for heteromeric gap junction formation
Connexin43 (Cx43) is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx), including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2013.00067/full |
| _version_ | 1819206245649743872 |
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| author | Richard David Veenstra Xianming eLin Eric C Beyer |
| author_facet | Richard David Veenstra Xianming eLin Eric C Beyer |
| author_sort | Richard David Veenstra |
| collection | DOAJ |
| description | Connexin43 (Cx43) is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx), including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT) domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT) peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2) specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj) voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH) peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH) peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system. |
| first_indexed | 2024-12-23T05:04:32Z |
| format | Article |
| id | doaj.art-6d80d6802e2243ce99aa2126ba3b1f36 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T05:04:32Z |
| publishDate | 2013-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6d80d6802e2243ce99aa2126ba3b1f362022-12-21T17:59:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122013-05-01410.3389/fphar.2013.0006747408Interfering amino terminal peptides and functional implications for heteromeric gap junction formationRichard David Veenstra0Xianming eLin1Eric C Beyer2SUNY Upstate Medical UniversitySUNY Upstate Medical UniversityUniversity of ChicagoConnexin43 (Cx43) is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx), including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT) domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT) peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2) specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj) voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH) peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH) peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.http://journal.frontiersin.org/Journal/10.3389/fphar.2013.00067/fullSperminegap junctionconnexin43connexin40Heteromeric channel |
| spellingShingle | Richard David Veenstra Xianming eLin Eric C Beyer Interfering amino terminal peptides and functional implications for heteromeric gap junction formation Frontiers in Pharmacology Spermine gap junction connexin43 connexin40 Heteromeric channel |
| title | Interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| title_full | Interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| title_fullStr | Interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| title_full_unstemmed | Interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| title_short | Interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| title_sort | interfering amino terminal peptides and functional implications for heteromeric gap junction formation |
| topic | Spermine gap junction connexin43 connexin40 Heteromeric channel |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2013.00067/full |
| work_keys_str_mv | AT richarddavidveenstra interferingaminoterminalpeptidesandfunctionalimplicationsforheteromericgapjunctionformation AT xianmingelin interferingaminoterminalpeptidesandfunctionalimplicationsforheteromericgapjunctionformation AT ericcbeyer interferingaminoterminalpeptidesandfunctionalimplicationsforheteromericgapjunctionformation |