Connexins in health and disease

Abstract

Gap junctions or hemichannels are expressed on all cells in our body, and have a highly significant role in homeostasis and in disease states. There are 21 connexins found in humans and they have distinct characteristics that compensate for each other. The anatomical expression pattern also differs between each connexin; some of them are expressed together and some are not. Genetically mutated connexin genes induce inheritable diseases, but acquired disorders can also be caused by primary or secondary connexin dysfunctions. In the central nervous system, glial cells are the main connexin-expressing cells. They utilize connexin gap junctions to assemble glial networks. The present review not only describes the basic structures and functions of connexins, it also examines the relationships between connexins and their role in disease pathology.

Retracted: Identification of de novo mutations in prenatal neurodevelopment-associated genes in schizophrenia in two Han Chinese patient-sibling family-based cohorts

“…Connexin 45 (Cx45) encoded by GJC1 is a component of the gap junction channel. It is one of the two connexin genes expressed predominantly in neurons 63 . Our analyzes showed that GJC1 was expressed highly in prenatal stage as compared to that in postnatal stage and was expressed predominantly in glutamatergic excitatory neurons in the human brain ( Fig.…”

Novel animal model of multiple sclerosis: The glial connexin gap junction as an environmental tuner for neuroinflammation

“…In the central nervous system (CNS), astroglia express Cx26, Cx30, and Cx43; oligodendroglia express Cx32, Cx47, and Cx29/Cx31.3; 7 microglia also express Cx43 when they are activated; and neurons express Cx36 to form electrical synapses 21 . Unlike astroglia and oligodendroglia, which form GJs between each cell type as well as each other, microglia and neurons do not form GJs 4 …”

“…Currently, 21 connexin gene family members have been discovered in humans (Table 1). 3,4 The connexin family is subdivided into five subfamilies (α, β, γ, δ, ε) based on the similarity of amino acid sequences 5 . Most cells have been found to express more than one member of the connexin family.…”

“…Two connexons form a GJ between cells via a head‐to‐head configuration in a homotypic or heterotypic manner (Figure 1). 4,6,7 Before the discovery of connexins, the half‐life of fully assembled GJs was estimated to be 5 hours 8 . Development of the more accurate method of pulse‐chase labeling of connexins with appropriate antibodies has revealed that most connexins have a half‐life of 1 to 2.5 hours from their synthesis to degradation 9 .…”

Oligodendroglial connexin 47 regulates neuroinflammation upon autoimmune demyelination in a novel mouse model of multiple sclerosis

“…Connexins (Cxs) are gap‐junction proteins organized as a hexagonal cylinder with a central pore. Gap junctions are ubiquitously expressed by all organs in the human body, including solid organs such as the liver, heart, skin, and kidneys as well as nonsolid organs such as white blood cells 2 . In the CNS, Cx30 and Cx43 are expressed on astroglia, and Cx32 and Cx47 are expressed on oligodendroglia.…”