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Interfering amino terminal peptides and functional implications for heteromeric gap junction formation
Eric C Beyer1, Xianming Lin, Richard D Veenstra
1Department of Pediatrics, University of Chicago Chicago, IL, USA.
Frontiers in Pharmacology
|June 5, 2013
Summary
Connexin43 (Cx43) interacts functionally with Cx37, Cx45, Cx46, and Cx50, but uniquely suppresses Cx40 gap junction function. This study investigates these connexin interactions and their implications for cardiac conduction.
Area of Science:
- Cell Biology
- Biophysics
- Cardiovascular Research
Background:
- Connexin43 (Cx43) is a key gap junction protein expressed in various human tissues.
- Cx43 co-expresses with other connexins (Cx), such as Cx40, Cx37, Cx45, Cx46, and Cx50, in specific organs.
- Functional implications of Cx43 heteromeric interactions with co-expressed connexins are significant but not fully understood, especially regarding Cx40.
Purpose of the Study:
- To investigate the functional heteromeric interactions between Connexin43 (Cx43) and other connexins, particularly Cx40.
- To elucidate the role of connexin amino-terminal (NT) domains in mediating these interactions.
- To assess the impact of these interactions on gap junction function and potential implications for cardiac conduction.
Main Methods:
- Utilized pentameric connexin sequence-specific NT domain interfering peptides (iNT) to probe interactions.
- Applied Cx43 and Cx40 iNT peptides to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions.
- Assessed electrical coupling and transjunctional voltage (Vj)-dependent inhibition of gap junction function.
Main Results:
- Cx43 iNT peptide specifically inhibited Cx40 gap junctions in a Vj-dependent manner, without affecting Cx37, Cx46, Cx50, and Cx45.
- A Cx40 iNT peptide counteracted the Vj-dependent block of Cx40 gap junctions.
- Cx50 iNT peptide did not counteract the block, suggesting interactions are not solely electrostatic.
Conclusions:
- Cx43 forms functional heteromeric gap junctions with Cx37, Cx45, Cx46, and Cx50.
- Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence.
- These findings highlight specific functional implications for Cx43-Cx40 heteromeric interactions in cardiac conduction.
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