Connexin 26 is a protein found throughout the human body, playing a fundamental part in how cells communicate directly. It belongs to the connexin family, which forms specialized channels between cells. This protein is particularly studied due to its significant connection to various biological processes, including normal hearing function.
How Connexin 26 Works in Cells
Connexin 26’s primary role involves forming structures known as gap junctions. These gap junctions are direct channels that connect the interiors of adjacent cells, allowing for the quick passage of small molecules, ions, and signaling molecules. This enables cells to share resources and information. This direct communication is achieved when six connexin proteins assemble to form a half-channel, called a connexon, on one cell’s membrane. This connexon then aligns with a connexon from a neighboring cell, creating a complete gap junction channel.
These channels are present in various tissues throughout the body, facilitating a wide range of cellular activities. For instance, gap junctions made with connexin 26 are known to specifically transport potassium ions and other small molecules. Such intercellular communication is a fundamental process for coordinating tissue development, maintaining cellular balance (homeostasis), and supporting diverse cellular functions.
Connexin 26 and Hearing Loss
Connexin 26 holds a notable role in the inner ear, particularly within the cochlea. The conversion of sound waves into electrical nerve impulses relies on the precise maintenance of ion levels in the inner ear fluids. Channels formed by connexin 26 are thought to help regulate these potassium ion levels. This ionic balance generates an electrical potential which drives the process of sound transduction.
Mutations in the GJB2 gene, which provides instructions for making connexin 26, can disrupt this delicate balance and lead to sensorineural hearing loss. These mutations can cause the connexin 26 protein to be altered, nonfunctional, or even absent, impairing the formation or activity of gap junctions in the inner ear. When potassium ion recycling is disrupted, the proper function and survival of cells necessary for hearing are affected, leading to hearing impairment. Mutations in GJB2 are a common genetic cause of non-syndromic hearing loss, accounting for approximately 50% of such cases in children.
Other Functions of Connexin 26
Beyond its prominent role in hearing, connexin 26 is expressed in numerous other tissues throughout the body, indicating its broader involvement in cellular processes. It is found in the skin, liver, brain, mammary gland, salivary gland, uterus, testes, pancreas, lungs, stomach, thyroid, and parathyroid. In the skin, connexin 26 contributes to the growth, maturation, and stability of the epidermis, the outermost layer of the skin.
Dysfunction of connexin 26 can contribute to certain skin disorders, sometimes alongside hearing loss. For example, specific GJB2 gene mutations are linked to conditions like Bart-Pumphrey syndrome, characterized by white nail discoloration, thickened skin on palms and soles, and hearing loss. Another condition, palmoplantar keratoderma with deafness, also involves thick skin on the hands and feet in addition to hearing impairment.
Genetic Aspects of Connexin 26 Mutations
The connexin 26 protein is encoded by the GJB2 gene. Most GJB2-related hearing loss follows an autosomal recessive inheritance pattern, meaning an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. If a person inherits only one mutated copy of the GJB2 gene, they are considered a carrier and typically do not experience hearing loss themselves.
When both parents are carriers of a GJB2 mutation, each child has a 25% chance of inheriting two copies of the mutated gene and developing hearing loss. There is also a 50% chance that their child will be a carrier, and a 25% chance that the child will inherit no mutated copies. Genetic testing can identify GJB2 mutations, which is particularly useful for diagnosing the cause of hearing loss and for genetic counseling, especially for families planning to have children.