Bridging the gap to therapeutic strategies based on connexin/pannexin biology

Abstract

A unique workshop was recently held focusing on enhancing collaborations leading to identify and update the development of therapeutic strategies targeting connexin/pannexin large pore channels. Basic scientists exploring the functions of these channels in various pathologies gathered together with leading pharma companies which are targeting gap junction proteins for specific therapeutic applications. This highlights how paths of discovery research can converge with therapeutic strategies in innovative ways to enhance target identification and validation.

Keywords: Connexins; Gap junctions; Pannexins; Peptides; Strategies; Therapeutics.

Fig. 1

Connexin and pannexin topology. Connexin and pannexin share a common structural topology despite the absence of sequence homology. Both are transmembrane proteins with four transmembrane domains, two extracellular loops, one cytoplasmic loop, and cytoplasmic N– and C–terminal domains (a, c). Connexin and pannexin monomers both oligomerize to form a functional ‘connexon’ and ‘pannexon’ channel, respectively. However, only connexin channels can assemble into a gap junction that allows intercellular communication. Pannexin is glycosylated and large glycan residues prevent the docking of pannexin channels from adjacent cells (b, d). The amino acid sequences in a and c represent human Cx43 and Panx1 respectively. PTMs post-translational modifications. Figure contributed by Dr. M. Le Vasseur, University of British Columbia, Canada

Fig. 2

Schmematic of Cx43 amino acid sequence showing portions of the protein which have been targeted with mimetic peptides. See text for details. The commonly used mimetic peptides, Gap26 and Gap 27, are shown for reference. Figure contributed by Dr. L. Leybaert, Ghent University, Belgium