Gap junctions, deafness & wound healing

A mutation in the gjb2 gene, which encodes the protein connexin 26 (Cx26) and is associated with deafness, has been implicated in wound healing. The findings were today reported to the European Society of Human Genetics in Amsterdam by Dr. Stella Man of the Institute of Cell and Molecular Sciences at London's Queen Mary University.

Connexin proteins are the main constituents of structures called gap junctions, which are involved in intercellular communication. Gap junctions form transmembrane channels which connect the cytoplasms of adjacent cells. The passage of ions through gap junctions electrically couples adjacent cells. This is especially useful in cardiac muscle because it enables heart cells to contract together.

fig6.jpg Diagram of gap junctions

Mutations in the gjb2 gene are the most common cause of genetic deafness; the association between the mutation and deafness was discovered in 1997 by Professor David Kelsell, who led the research team. The exact reason why gjb2 mutations is unknown, although it probably has something to do with disrupted electrical coupling between cells in the inner ear, whose function is to transduce soundwaves into electrical signals which are sent to the brain.

Dr. Man, Professor Kelsell and their colleagues have been investigating one of the gjb2 mutations. With the knowledge that the gjb2 is active in skin cells, the team developed a laboratory model of the skin to try and determine the role of the protein in this tissue.

"We decided to investigate how the mutation affected the ability of cells to communicate with each other in the epidermis where Cx26 is also expressed," said Dr. Man, "[and] we found that it was directly associated with wound healing and bacterial invasion."

The findings explain why gjb2 mutations have been conserved in evolution. While having two copies of the mutated gene results in deafness, having one copy confers an advantage – improved wound healing and, perhaps reduced susceptibility to bacterial infection. A similar situation occurs in sickle cell anemia; two defective copies of the haemoglobin gene result in the condition, while one defective copy provides resistance to malaria.