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(Circulation Research. 2007;101:1283.)
© 2007 American Heart Association, Inc.

Cellular Biology

C-Terminal Truncation of Connexin43 Changes Number, Size, and Localization of Cardiac Gap Junction Plaques

Karen Maass, Junko Shibayama, Sharon E. Chase, Klaus Willecke, Mario Delmar

From the SUNY Upstate Medical University (K.M., J.S., S.E.C., M.D.), Syracuse, NY; and the Institut für Genetik (K.W.), Universität Bonn, Germany.

Correspondence to Mario Delmar, MD, PhD, Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210. E-mail delmarm{at}upstate.edu

Haplodeficient mice expressing carboxyl-terminally truncated Cx43 (K258stop/KO), instead of the wild-type Cx43 isoform, reach adulthood and reveal no abnormalities in heart morphology. Here, we have analyzed the expression of K258stop protein and the morphology of gap junctions in adult hearts of these mice. Coimmunofluorescence analysis revealed reduced juxtaposition of K258stop with other junctional proteins at the intercalated disc. Immunoprecipitation studies documented changes in the interaction with previously described Cx43 binding proteins. Quantitative transmission electron and confocal microscopy confirmed the localization of K258stop gap junctions to the periphery of the intercalated disc and further revealed an increase in the size of K258stop gap junction plaques and a reduction in their number. Dual whole cell patch clamp analysis confirmed that K258stop gap junctions were functional, with single channel properties similar to those described in exogenous systems. We conclude that the carboxyl-terminal domain of Cx43 (Cx43CT) is involved in regulating the localization, number and size of Cx43 plaques in vivo. Conversely, protein interactions or posttranslational modifications taking place within the Cx43CT are not required for the assembly of functional gap junctions in the intercalated disc.

Key Words: gap junctions • connexin43 • heart • intercalated disc

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The Carboxy Terminal Domain of Connexin43: From Molecular Regulation of the Gap Junction Channel to Supramolecular Organization of the Intercalated Disk

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