Gap junctions (GJ) provide intercellular communication in species as evolutionary distant as hydra and men. They are known as ancient cell junctions forming membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasm of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in almost all tissues. In addition, substantial evidence has accumulated during the last decade supporting a more expanded repertoire of functions beyond direct cell-to-cell communication. Today, connexins and the second family of GJ-type proteins, the pannexins (Panx) are known to form functional gap junctions (Cx), (hemi)channels (Cx), and channels only (Panx) allowing direct communication between cells and between cells and the extracellular environment. Most recently, evidence for non-channel functions have been reported, suggesting that GJ type proteins can be functional even without establishing channels. In light of the expression diversity, a complex life cycle and a multitude of functions it is not surprising that dysfunctional GJ communication (GJC) was linked to human disease. Genetic approaches are uncovering a fast growing number of mutations in Cxs, which are correlated to human diseases including deafness, skin disease, peripheral and central neuropathies, cataracts, or cardiovascular dysfunctions. This provides an unequivocal demonstration that GJC is crucial for diverse physiological processes throughout the human body. Furthermore, connexins and pannexins are discussed in a wide spectrum of conditions including, but not limited to cancer, stroke, epilepsy, schizophrenia or autism. The focus of this review topic will be on delineating the most recent developments and technological advancements in the GJ field, highlighting the fast pacing discovery of dysfunctional GJC in congenital or acquired human disease.
Gap junctions (GJ) provide intercellular communication in species as evolutionary distant as hydra and men. They are known as ancient cell junctions forming membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasm of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in almost all tissues. In addition, substantial evidence has accumulated during the last decade supporting a more expanded repertoire of functions beyond direct cell-to-cell communication. Today, connexins and the second family of GJ-type proteins, the pannexins (Panx) are known to form functional gap junctions (Cx), (hemi)channels (Cx), and channels only (Panx) allowing direct communication between cells and between cells and the extracellular environment. Most recently, evidence for non-channel functions have been reported, suggesting that GJ type proteins can be functional even without establishing channels. In light of the expression diversity, a complex life cycle and a multitude of functions it is not surprising that dysfunctional GJ communication (GJC) was linked to human disease. Genetic approaches are uncovering a fast growing number of mutations in Cxs, which are correlated to human diseases including deafness, skin disease, peripheral and central neuropathies, cataracts, or cardiovascular dysfunctions. This provides an unequivocal demonstration that GJC is crucial for diverse physiological processes throughout the human body. Furthermore, connexins and pannexins are discussed in a wide spectrum of conditions including, but not limited to cancer, stroke, epilepsy, schizophrenia or autism. The focus of this review topic will be on delineating the most recent developments and technological advancements in the GJ field, highlighting the fast pacing discovery of dysfunctional GJC in congenital or acquired human disease.
