Innexins are a family of proteins that form channels allowing for direct communication between adjacent cells. These proteins are integral to the cell membrane, creating a pathway for the exchange of small molecules and ions. This intercellular communication is a feature of multicellular organisms, and innexins provide the structural basis for this process in invertebrates.
The Structure and Function of Innexins
Innexin proteins have a specific molecular architecture that allows them to perform their communication role. Each protein spans the cell membrane four times, resulting in four transmembrane segments. This configuration leaves both the start (N-terminus) and end (C-terminus) of the protein chain inside the cytoplasm and creates two loops exposed to the space between cells.
Individual innexin proteins assemble into a larger complex. In invertebrates, eight innexins come together in a cell’s membrane to form a structure called an innexon, or hemichannel. This octameric arrangement creates a pore in the cell’s membrane.
For communication to occur, an innexon from one cell must connect with an innexon from a neighboring cell. When two innexons align and dock, they form a complete gap junction channel. This channel functions as a direct bridge, allowing the passive diffusion of ions and small signaling molecules between the connected cells.
Innexins in Invertebrate Biology
Innexins are the primary proteins that form gap junctions in invertebrate animals, with their importance documented in model organisms like the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. The C. elegans genome contains 25 distinct innexin genes, while Drosophila has eight, highlighting the diverse roles these proteins play.
In C. elegans, different innexins are expressed in specific tissues and at different life stages. For example, innexins UNC-7 and UNC-9 are necessary for coordinated movement by ensuring proper communication at neuromuscular junctions. Other innexins are involved in the reproductive system, such as INX-14, which helps guide sperm. The specific expression patterns suggest that different innexin combinations may form channels with distinct properties.
In Drosophila, innexins are also central to development and physiology. The innexin known as Inx2 is involved in forming the wing epithelium by allowing transport of signaling molecules between cells. In the nervous system, innexins form electrical synapses that allow for rapid transmission of nerve impulses.
Comparing Innexins to Connexins and Pannexins
Innexins are the basis of gap junctions in invertebrates, while vertebrates use a different family of proteins called connexins for the same purpose. Although innexins and connexins perform the same function, they do not share significant amino acid sequence similarity. This suggests they are the product of convergent evolution, where different proteins evolved to solve the same biological problem.
Structurally, both protein families have a similar membrane topology with four transmembrane domains. A difference lies in their assembly; invertebrate innexons are typically formed from eight protein subunits, whereas vertebrate connexons are made of six. This results in an innexin gap junction channel being composed of 16 total subunits, compared to 12 for a connexin channel.
A third family, pannexins, are found in vertebrates and are evolutionarily related to invertebrate innexins. Despite this relationship, pannexins do not typically form gap junctions. Instead, they primarily function as single membrane channels, or hemichannels, allowing molecules like ATP to pass between the cell’s cytoplasm and the extracellular environment.
Significance in Research and Disease Models
Because invertebrates like C. elegans and Drosophila have well-understood genetics and are easy to manipulate, scientists can readily study the consequences of mutations in innexin genes. These findings have direct relevance to human health.
Mutations in human connexin genes, which are analogous to innexins, are responsible for a range of genetic disorders called connexinopathies. These can include certain forms of congenital deafness, skin diseases, and cataracts.
By studying what goes wrong when an innexin gene is altered in a worm or fly, researchers can better understand the cellular mechanisms disrupted in human connexin-related diseases. For example, observing locomotion defects in a C. elegans mutant with a faulty innexin provides clues about how faulty connexins might affect neural or muscle tissue in humans. In this way, invertebrate innexins serve as valuable experimental models to explore the consequences of impaired gap junction function.