Connexin (Gap junction protein) (Cx)

Connexins are a family of 21 transmembrane proteins in humans that are essential for direct intercellular communication and tissue homeostasis [1, 10]. They assemble into hexameric structures called hemichannels or connexons, which can function independently or dock with hemichannels from adjacent cells to form gap junctions [12, 16]. These junctions allow the passage of ions, metabolites, and small signaling molecules like cAMP and IP3 between neighboring cells, coordinating physiological activities such as cardiac contraction and embryonic development [1, 12]. Dysregulation of connexin expression or function is implicated in a wide range of diseases, including cardiac arrhythmias, neurodegenerative disorders, chronic skin wounds, and various cancers [1, 4, 10]. In oncology, connexins exhibit a complex dual role, acting as tumor suppressors in early stages but potentially promoting metastasis in advanced disease [4, 7, 14]. Pharmacological targeting of connexins involves small molecules and peptide mimetics designed to either block pathological hemichannel opening or enhance gap junctional communication [1, 2, 11]. Current therapeutic challenges include achieving isoform specificity and managing off-target effects due to the ubiquitous distribution of these proteins across different organ systems [1, 6].

Other names

Gap junction proteinGJPConnexon subunitGJAGJBGJCGJDGJE

Modulation of gap junctional intercellular communication (GJIC) and hemichannel activity through pore blockade, gating modification, or stabilization of channel assembly.