Connexin family (Cx)

The Connexin family comprises a group of 21 transmembrane proteins in humans that are the primary components of gap junctions, which facilitate direct communication between adjacent cells (Laird & Lampe, 2018) [1.2.1]. These proteins assemble into hexameric structures called connexons or hemichannels; when two connexons from neighboring cells dock, they form a continuous aqueous pore allowing the exchange of ions, metabolites, and small signaling molecules (Wikipedia) [1.1.2]. This intercellular communication is vital for coordinating physiological activities such as the synchronous contraction of the heart, neuronal signaling, and embryonic development (Beyer & Berthoud, 2017) [1.1.1]. Mutations in connexin genes are associated with diverse hereditary conditions, including sensorineural hearing loss, cataracts, and various skin and neurological disorders (NIH) [1.2.1]. In the context of pharmacology, connexins are targeted to treat conditions like cardiac arrhythmias, chronic wounds, and certain cancers, where they can act as either tumor suppressors or facilitators of metastasis (MDPI) [1.2.2]. Current therapeutic approaches involve small molecule inhibitors, peptide mimetics, and enhancers that modulate channel gating or assembly, though achieving isoform specificity remains a significant hurdle due to the high structural similarity and widespread expression of family members (Verselis & Srinivas, 2013) [1.3.4].

Other names

Gap junction proteinConnexonGJAGJBGJCGJDGJE

Modulation of gap junctional intercellular communication (GJIC) and hemichannel activity through pore blockade, gating modification (e.g., loop gating), or regulation of protein-protein interactions, trafficking, and stability (NIH) [1.3.1, 1.3.4].