Mechanisms of Connexin Regulating Peptides

• Type of Material: Article
• Authors: Ryan D King, Virginia Tech; Meghan W Sedovy, Virginia Tech; Xinyan Leng, Virginia Tech; Jianxiang Xue, University of Virginia; Samy Lamouille, Virginia Tech; Michael Koval, Emory University; Brant E Isakson, University of Virginia; Scott R Johnstone, Virginia Tech
• Language: English
• Date: 2021-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms221910186
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 22
• Issue: 19
• Grant/Funding Information: This research was funded by AHA-CDA 19CDA34630036 (S.R.J.), NIH R01-AA025854 (M.K.), NIH R01-HL137112 (B.E.I., M.K.).
• Keywords: PROTEIN-KINASE-C; PANNEXIN CHANNELS; pannexin; ISCHEMIA/REPERFUSION INJURY; MIMETIC PEPTIDES; gap junction; BIOPHYSICAL PROPERTIES; peptide; ANTIARRHYTHMIC PEPTIDE; ZONULA OCCLUDENS-1; CARBOXYL-TERMINAL DOMAIN; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Physical Sciences; hemichannel; cell signaling; connexin; SRC FAMILY KINASES; Life Sciences & Biomedicine; Science & Technology; GAP JUNCTIONAL COMMUNICATION; Chemistry

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.