Peptides Targeting Gap Junctional Structures

Jean-Claude      Herve; Stefan      Dhein

doi:10.2174/138161210793292528

Abstract

Cells of multicellular organisms need to communicate and have evolved different mechanisms of intercellular communication, the most direct and quickest of which is through channels that directly link the cytoplasms of adjacent cells. In metazoans, intercellular channels result from the docking of two hemichannels, hexameric torus of junctional proteins (connexins being the most known) around an aqueous pore. Junctional channels and hemichannels are not passive conduits as they had been regarded for a long time but their permeability is finely tuned by complex mechanisms that have just begun to be identified, the delay being partly due to limited availability of specific pharmacological tools. Peptides have a number of advantages over other molecules in terms of specificity and affinity for targets. Some of them interact with membrane receptors, activating a signaling transduction cascade leading to modifications in the expression of gap junctional proteins or the functional state of channels. A second approach is based on the use of so-called mimetic peptides (also known as gap peptides) that mimic a short sequence of gap junction proteins and have been shown to attenuate processes downstream of the putative channel activity. They also represent very useful tools to investigate the structure of domains of gap junction proteins. This review presents an overview of the literature on peptides targeting gap junctional structures.

Keywords: Gap junction, connexines, hemichannels, antiarrhythmic peptides, endothelin, angiotensin, arrhythmia, mimetic peptides