Gap junction beta-1 protein (GJB1), also known as connexin 32 (Cx32), is a transmembrane protein that in humans is encoded by the GJB1 gene. Gap junction beta-1 protein is a member of the gap junction connexin family of proteins that regulates and controls the transfer of communication signals across cell membranes, primarily in the liver and peripheral nervous system. However, the protein is expressed in multiple organs, including in oligodendrocytes in the central nervous system. Mutations of the GJB1 gene affecting the signalling of and trafficking through gap junctions, resulting in an inherited peripheral neuropathy called X-linked Charcot-Marie-Tooth Disease. Complications include the demyelination of oligodendrocytes and Schwann cells, causing delayed transmission rates of nerve communication in the peripheral nervous system, due to irregularities in the normal function of the cells. This condition leads to a number of symptoms, most commonly muscle weakness and sensory problems in the outer extremities of the limbs. As a result, muscle atrophy and soft tissue injuries due to delayed nerve transmission can occur. In males, due to the hemizygousity of the X-chromosome, the symptoms and issues surrounding X-linked Charcot-Marie-Tooth disease are more prevalent.
Function Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and small molecules between cells. For a general discussion of connexin proteins, see GJB2. In Schwann cells, GJB1 also forms channels that facilitate transfers between layers of the myelin. In melanocytic cells GJB1 gene expression may be regulated by MITF.
Gene The gene that encodes the human GJB1 protein is found on the X chromosome, on the long arm at position q13.1, in interval 8, from base pair 71,215,212 to base pair 71,225,215.
Mutations Approximately four hundred mutations within the GJB1 gene have been identified as causing type X Charcot-Marie-Tooth disease, and it is the only gene known to be associated with this disease. The majority of these mutations only change a single amino acid within the protein chain, which result in a different protein being produced. Mutations within the GJB1 gene consist of novel, missense, double-missense, amino acid deletion, nonsense, frameshift, and in-frame deletions/insertions. These mutations most commonly result in proteins that work incorrectly, less effectively, degrade faster, are not present in adequate numbers or may not function at all.
Structure The GJB1 gene is approximately 10kb in length, with one coding exon and three non-coding exons. GJB1 is a gap junction, beta 1 protein also identified as connexin 32, with 238 amino acids. This protein contains four transmembrane domains, which when assembled form gap junctions. Each of these gap junctions consist of two hemichannels (connexions), which in turn consist of six connexin molecules (gap junction trans-membrane proteins)., A picture of a connexin and its connexons, showing the two hemichannels, is available here: https://commons.wikimedia.org/wiki/File:Connexon_and_connexin_structure.svg. This enables communication between Schwann cell nuclei and axons through a radial diffusion pathway. As noted above, channels also form between layers of myelin.
Function GJB1 functions as a radial diffusion pathway, allowing the communication and diffusion of nutrients, ions and small molecules between cells, and between layers of myelin. The GJB1 protein is found in a number of organs, including the liver, kidney, pancreas and nervous system. In normal circumstances this protein is located in the cell membrane of Schwann cells and oligodendrocytes, specialised cells of the nervous system. These cells typically encapsulate nerves and are involved in the assembly and preservation of myelin, which serves to ensure reliable and rapid transmission of nerve signals. Typically the GJB1 protein forms channels between cells as well as through myelin to the internal Schwann cell or oligodendrocyte, allowing effective transportation and communication.
… excerpt ends here. Continue reading the full article.
