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Managing the Complexity of Communication: Regulation of Gap Junctions by Post-translational Modification

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Journal Front Pharmacol
Date 2013 Oct 25
PMID 24155720
Citations 63
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Abstract

Gap junctions are comprised of connexins that form cell-to-cell channels which couple neighboring cells to accommodate the exchange of information. The need for communication does, however, change over time and therefore must be tightly controlled. Although the regulation of connexin protein expression by transcription and translation is of great importance, the trafficking, channel activity and degradation are also under tight control. The function of connexins can be regulated by several post translational modifications, which affect numerous parameters; including number of channels, open probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated, acetylated, methylated, and γ-carboxyglutamated. The aim of the present review is to summarize our current knowledge of post translational regulation of the connexin family of proteins.

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References
1.
Lampe P, Lau A . Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys. 2001; 384(2):205-15. DOI: 10.1006/abbi.2000.2131. View

2.
Lau A, Kanemitsu M, Kurata W, Danesh S, Boynton A . Epidermal growth factor disrupts gap-junctional communication and induces phosphorylation of connexin43 on serine. Mol Biol Cell. 1992; 3(8):865-74. PMC: 275645. DOI: 10.1091/mbc.3.8.865. View

3.
Stenflo J, Fernlund P, Egan W, Roepstorff P . Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci U S A. 1974; 71(7):2730-3. PMC: 388542. DOI: 10.1073/pnas.71.7.2730. View

4.
Sirnes S, Leithe E, Rivedal E . The detergent resistance of Connexin43 is lost upon TPA or EGF treatment and is an early step in gap junction endocytosis. Biochem Biophys Res Commun. 2008; 373(4):597-601. DOI: 10.1016/j.bbrc.2008.06.095. View

5.
Bao M, Kanter E, Huang R, Maxeiner S, Frank M, Zhang Y . Residual Cx45 and its relationship to Cx43 in murine ventricular myocardium. Channels (Austin). 2011; 5(6):489-99. PMC: 3265797. DOI: 10.4161/chan.5.6.18523. View