Mechanisms of Connexin Regulating Peptides

doi:10.3390/ijms221910186

Review

. 2021 Sep 22;22(19):10186.

doi: 10.3390/ijms221910186.

Mechanisms of Connexin Regulating Peptides

D Ryan King¹, Meghan W Sedovy^{1

2}, Xinyan Leng¹, Jianxiang Xue³, Samy Lamouille^{1

4}, Michael Koval⁵, Brant E Isakson^{3

6}, Scott R Johnstone^{1

4

7}

Affiliations

¹ Fralin Biomedical Research Institute at Virginia Tech Carilion School of Medicine, Virginia Tech, Roanoke, VA 24016, USA.
² Translational Biology, Medicine, and Health Graduate Program, Virginia Tech, Blacksburg, VA 24061, USA.
³ Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁴ Center for Vascular and Heart Research, Virginia Tech, Roanoke, VA 24016, USA.
⁵ Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁶ Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁷ Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24060, USA.

PMID: 34638526
PMCID: PMC8507914
DOI: 10.3390/ijms221910186

Review

Mechanisms of Connexin Regulating Peptides

D Ryan King et al. Int J Mol Sci. 2021.

. 2021 Sep 22;22(19):10186.

doi: 10.3390/ijms221910186.

Authors

D Ryan King¹, Meghan W Sedovy^{1

2}, Xinyan Leng¹, Jianxiang Xue³, Samy Lamouille^{1

4}, Michael Koval⁵, Brant E Isakson^{3

6}, Scott R Johnstone^{1

4

7}

Affiliations

¹ Fralin Biomedical Research Institute at Virginia Tech Carilion School of Medicine, Virginia Tech, Roanoke, VA 24016, USA.
² Translational Biology, Medicine, and Health Graduate Program, Virginia Tech, Blacksburg, VA 24061, USA.
³ Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁴ Center for Vascular and Heart Research, Virginia Tech, Roanoke, VA 24016, USA.
⁵ Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁶ Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁷ Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24060, USA.

PMID: 34638526
PMCID: PMC8507914
DOI: 10.3390/ijms221910186

Abstract

Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies over the last 60 years have demonstrated the utility of altering GJ signaling pathways in experimental models, which has led to them being attractive targets for therapeutic intervention. A number of different mechanisms have been proposed to regulate GJ signaling, including channel blocking, enhancing channel open state, and disrupting protein-protein interactions. The primary mechanism for this has been through the design of numerous peptides as therapeutics, that are either currently in early development or are in various stages of clinical trials. Despite over 25 years of research into connexin targeting peptides, the overall mechanisms of action are still poorly understood. In this overview, we discuss published connexin targeting peptides, their reported mechanisms of action, and the potential for these molecules in the treatment of disease.

Keywords: cell signaling; connexin; gap junction; hemichannel; pannexin; peptide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Schematic of the Cx43 protein in the plasma membrane with colored lines indicating the positions of described peptides targeting EL, IL, and CT regions.

See this image and copyright information in PMC

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References

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[1] Revel J.P., Karnovsky M.J. Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J. Cell Biol. 1967;33:C7–C12. doi: 10.1083/jcb.33.3.C7. - DOI - PMC - PubMed

[2] Revel J.P., Karnovsky M.J. Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J. Cell Biol. 1967;33:C7–C12. doi: 10.1083/jcb.33.3.C7. - DOI - PMC - PubMed

[3] Dewey M.M., Barr L. Intercellular Connection between Smooth Muscle Cells: The Nexus. Science. 1962;137:670–672. doi: 10.1126/science.137.3531.670-a. - DOI - PubMed

[4] Dewey M.M., Barr L. Intercellular Connection between Smooth Muscle Cells: The Nexus. Science. 1962;137:670–672. doi: 10.1126/science.137.3531.670-a. - DOI - PubMed

[5] Robertson J.D. The occurence of a subunit pattern in the unit membranes of club endings in mauthner cell synapses in goldfish brains. J. Cell Biol. 1963;19:201–221. doi: 10.1083/jcb.19.1.201. - DOI - PMC - PubMed

[6] Robertson J.D. The occurence of a subunit pattern in the unit membranes of club endings in mauthner cell synapses in goldfish brains. J. Cell Biol. 1963;19:201–221. doi: 10.1083/jcb.19.1.201. - DOI - PMC - PubMed

[7] Evans W.H., Martin P.E. Gap junctions: Structure and function (Review) Mol. Membr. Biol. 2002;19:121–136. doi: 10.1080/09687680210139839. - DOI - PubMed

[8] Evans W.H., Martin P.E. Gap junctions: Structure and function (Review) Mol. Membr. Biol. 2002;19:121–136. doi: 10.1080/09687680210139839. - DOI - PubMed

[9] Johnstone S., Isakson B., Locke D. Biological and biophysical properties of vascular connexin channels. Int. Rev. Cell Mol. Biol. 2009;278:69–118. doi: 10.1016/S1937-6448(09)78002-5. - DOI - PMC - PubMed

[10] Johnstone S., Isakson B., Locke D. Biological and biophysical properties of vascular connexin channels. Int. Rev. Cell Mol. Biol. 2009;278:69–118. doi: 10.1016/S1937-6448(09)78002-5. - DOI - PMC - PubMed

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Mechanisms of Connexin Regulating Peptides

Affiliations

Mechanisms of Connexin Regulating Peptides

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Affiliations

Abstract

Conflict of interest statement

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