connexins

Connexins are a family of transmembrane proteins that assemble into gap junction channels, allowing direct exchange of ions and small molecules between neighboring cells. Through these channels, electrical and metabolic coupling supports coordinated cell activity and tissue homeostasis.

Each connexin protein has four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini. Six connexin subunits form a hemichannel, or connexon; two connexons from adjacent cells dock to create a complete gap junction channel. Channels can be homomeric/homotypic or heteromeric/heterotypic, which affects their conductance and permeability.

In humans, connexins are encoded by the GJA and GJB gene families (gap junction protein alpha and beta). Notable members include GJA1 (Cx43), GJA8 (Cx50), GJA3 (Cx46), GJB2 (Cx26), and GJB1 (Cx32). The family is diverse, with multiple genes expressed in different tissues and developmental stages.

Expression is widespread but tissue-specific, with high levels in heart, brain, lens, skin, and kidney. Connexins enable synchronized cardiac contraction, neuronal signaling, and maintenance of tissue homeostasis. They participate in development, wound healing, and response to cellular stress.

Mutations or dysregulation of connexins can cause diseases known as connexinopathies. Examples include GJB2-related deafness, GJB1-related neuropathies, and GJA1-related oculodentodigital dysplasia. Research on pharmacological modulators and connexin-mimetic peptides continues to explore therapeutic potential.