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4.12:

Gap Junctions

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Biology
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JoVE Core Biology
Gap Junctions

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Gap junctions are specialized membrane proteins that form channels between the cytoplasm of animal cells. They contribute to intercellular signaling by allowing the exchange of ions, second messengers, sugars, and other small molecules. These intercellular channels are composed of transmembrane proteins called connexins, or CX for short. Six connexins form a hemichannel, one half of a full channel, called a connexon. When all six proteins are the same, the connexon is considered to be homomeric. For instance, a prominent connexin in the heart, CX40, can form homomeric connexons. However, CX40 can also combine with a different heart connexin, CX43, to create a heteromeric version that may have different functions. such as selectivity for different molecules.

Connexons are formed in the Golgi apparatus and delivered to the cell membrane, where they partner up with connexons on adjacent neighboring cells to complete the channel. They often form clusters called gap junction plaques where the channels are continually recycled. Gap junctions are generally kept in an open state, but they can be closed under specific conditions. For instance, in the presence of calcium, the “petals” of the connexins rotate inwards, which closes the channel. Such actions are important in heart cells, called cardiomyocytes, which use gap junctions to electrically couple groups of cells together to generate synchronized rhythmic contractions.

4.12:

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.

Suggested Reading

Laird, Dale W., Christian C. Naus, and Paul D. Lampe. "SnapShot: Connexins and disease." Cell 170, no. 6 (2017): 1260-1260. [Source]

Vinken, Mathieu. "Introduction: connexins, pannexins and their channels as gatekeepers of organ physiology." Cellular and Molecular Life Sciences 72, no. 15 (2015): 2775-2778. [Source]