4.14 : Gap Junctions

Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and skin disorders.

Vertebrate gap junctions are composed of transmembrane proteins called connexins (CX), and six connexins form a hemichannel called a connexon. Humans have at least 21 different forms of connexins that are expressed in almost all cell types. A connexon hemichannel is said to be homomeric when all six connexins are the same, and heteromeric when composed of different types.

Most cells express more than one type of connexin. These can form functional connexon hemichannels or a full gap junction channel by pairing up with a counterpart on an adjacent cell. The gap junctions are considered homotypic when each connexon is the same, and heterotypic when they differ. Clusters called gap junction plaques often form where the channels are continually recycled and degraded at the center of the plaques and replaced at the periphery.

Gap junctions allow the passage of ions, second messengers, sugars, and other small molecules between cells. This exchange is selectively permeable and determined by the connexin composition of the channel. They possess the ability, under certain conditions, to switch between open and closed states, allowing cells to regulate the exchange of molecules between them. Factors such as pH and the presence of Ca²⁺ ions can regulate the communication between cells on a shorter time scale, while differential gene expression controls the type and abundance of connexins in the various cell types in developmental and adult tissues.