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Gap junctions are specialized membrane channels between neighboring animal cells. They support intercellular signaling by allowing the exchange of ions, second messengers, sugars, and other small molecules between cells.
These channels are made of transmembrane proteins called connexins, or CX proteins.
Six connexin molecules assemble into a hemichannel, also called a connexon. A connexon makes up one half of a complete gap junction channel.
Connexons can be classified into two types: homomeric and heteromeric. When all six connexins are the same type, the structure is called a homomeric connexon.
For instance, in the heart, CX40 can form homomeric connexons. However, CX40 can also combine with another heart connexin, CX43, to form a heteromeric connexon. This heteromeric connexon may have different functions, such as selectivity for specific molecules.
Connexins are first made in the rough endoplasmic reticulum. Many connexins then move to the Golgi apparatus, where they assemble into connexons. The cell then transports the connexons to the plasma membrane. There, they pair with connexons from neighboring cells.
Together, the two hemichannels form a complete gap junction channel that directly connects the cytoplasm of both cells.
Many of these channels cluster together to form structures called gap junction plaques.
In many tissues, gap junction channels remain open under normal conditions, allowing continuous communication between cells.
In the heart, this open state is essential. Gap junctions allow electrical signals to spread rapidly from one cell to the next. Because ions move directly between neighboring cells, large groups of cardiomyocytes contract together in a coordinated, rhythmic pattern.
However, gap junctions are not permanently open. For example, when intracellular calcium levels rise, conformational changes in the connexin proteins cause the channel to close.
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Q1: What are gap junctions and what do they do between cells?
Gap junctions are specialized membrane channels that connect neighboring animal cells, allowing direct communication between their cytoplasm. They enable the exchange of ions, second messengers, sugars, and other small molecules. This intercellular signaling is essential for coordinated cellular functions across tissues and multicellular organisms.
Q2: How are connexins organized to form a complete gap junction channel?
Six connexin proteins assemble into a hemichannel called a connexon. Two connexons, one from each neighboring cell, pair together to form a complete gap junction channel. These channels cluster into structures called gap junction plaques, which facilitate continuous communication between cells.
Q3: What is the difference between homomeric and heteromeric connexons?
Homomeric connexons contain six identical connexin proteins, while heteromeric connexons combine different types of connexins. For example, heart cells can form homomeric connexons with CX40 alone or heteromeric connexons by combining CX40 with CX43. Heteromeric connexons may have different selectivity for specific molecules.
Q4: Where are connexins synthesized and how do they reach the plasma membrane?
Connexins are first synthesized in the rough endoplasmic reticulum. They then move to the Golgi apparatus, where they assemble into connexons. The cell transports these connexons to the plasma membrane, where they pair with connexons from neighboring cells to form functional gap junction channels.
Q5: Why are gap junctions critical for heart function?
Gap junctions in the heart allow electrical signals to spread rapidly between cardiomyocytes through direct ion movement. This enables large groups of heart cells to contract together in a coordinated, rhythmic pattern. Under normal conditions, gap junctions remain open to maintain continuous communication essential for proper heartbeat.
Q6: How do gap junctions regulate the exchange of molecules between cells?
Gap junctions possess the ability to switch between open and closed states, allowing cells to regulate molecular exchange. When intracellular calcium levels rise, conformational changes in connexin proteins cause channels to close. This selective permeability is determined by the connexin composition of the channel.
Q7: How many types of connexins exist in humans and where are they expressed?
Humans have at least 21 different forms of connexins expressed in almost all cell types. Most cells express more than one connexin type, which can form functional connexon hemichannels or complete gap junction channels. Differential gene expression controls the type and abundance of connexins in various tissues during development and adulthood.