Connexon

In biology, a connexon, also known as a connexin hemichannel, is an assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells. This channel allows for bidirectional flow of ions and signaling molecules. The connexon is the hemichannel supplied by a cell on one side of the junction; two connexons from opposing cells normally come together to form the complete intercellular gap junction channel. However, in some cells, the hemichannel itself is active as a conduit between the cytoplasm and the extracellular space, allowing the transference of ions and small molecules lower than 1-2 KDa. Little is known about this function of connexons besides the new evidence suggesting their key role in intracellular signaling. In biology, a connexon, also known as a connexin hemichannel, is an assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells. This channel allows for bidirectional flow of ions and signaling molecules. The connexon is the hemichannel supplied by a cell on one side of the junction; two connexons from opposing cells normally come together to form the complete intercellular gap junction channel. However, in some cells, the hemichannel itself is active as a conduit between the cytoplasm and the extracellular space, allowing the transference of ions and small molecules lower than 1-2 KDa. Little is known about this function of connexons besides the new evidence suggesting their key role in intracellular signaling. Connexons made of the same type of connexins are considered homomeric, while connexons made of differing types of connexins are heteromeric. The assembly of connexons begins with synthesis of connexins within the cell and ends with the formation of gap junction channel plaques on the cell membrane. The connexin subunit proteins that make up connexons are synthesized on the membranes of the cells endoplasmic reticulum. These subunits are then oligomerized, or combined with other smaller parts, into connexons in the golgi apparatus. The connexons are then delivered to their proper location on the plasma membrane. Connexons then dock with compatible connexons from the neighboring cell to form gap junction channel plaques. A large part of this process is mediated by phosphorylation of different enzymes and proteins, allowing and preventing interaction between certain proteins. Connexons contribute to the formation of gap junctions, and are an essential component of the electric synapses in neural pathways. In a single gap junction, connexons will assemble around an aqueous porous membrane, forming a hemi-channel that is composed of connexins. Connexins are the smaller protein molecules that make up connexons and play a crucial part to the formation of gap junctions. Structurally, connexins are made up of 4 alpha helical transmembrane domains connected by 2 extracellular loops and 1 cytoplasmic loop, while both N and C terminals reside intracellularly. Connexin types can be further differentiated by using their predicted molecular weight (ex: Connexin 43 is Cx 43 due to its molecular weight of 43 kDa). Connexons will form the gap junction by docking a hemi-channel to another hemi-channel in an adjacent cell membrane. During this phase, the formation of an intercellular channels spanning both of the plasma membranes, occurs. Subsequently, this process leads to a better understanding of how electric synapses are facilitated between neurons. Connexon structure is degraded by its removal from the plasma membrane. Connexons will be internalized by the cell itself as a double membrane channel structure (due to the docking of hemi-channels). This is called internalization or endocytosis. Research suggests that gap junctions in general may be internalized using more than one method, but the best known and most studied would be that of clathrin-mediated endocytosis. In simple terms this process consists of a ligand binding to a receptor signaling for a certain part of the membrane to be coated in clathrin. This part of the membrane then buds into the cell forming a vesicle. Now present in the cell membrane, connexons will be degraded by lysosomal pathways. Lysosomes are able to break down the proteins of the connexon because they contain specific enzymes that are made specifically for this process. It is thought that ubiquitination signals degradation within the cell. The properties of individual connexin proteins determine the overall properties of the whole connexon channel. The permeability and selectivity of the channels is determined by its width as well as the molecular selectivity of connexins such as charge selectivity. Research shows connexons are particularly permeable to soluble second messengers, amino acids, nucleotides, ions and glucose. Channels are also voltage sensitive. The connexon channels have voltage-dependent gates that open or close depending on the difference in voltage between the interiors of the two cells. Gates can also show voltage sensitivity depending on the difference in voltage from the interior and exterior of the cell (i.e. membrane potential).