Innexins are

transmembrane proteins A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

that form

gap junction Gap junctions are membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions'' alongside tight ...

s in

invertebrate Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordata, chordate s ...

s. Gap junctions are composed of

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

s that form a channel permeable to ions and small molecules connecting the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

of adjacent cells. Although gap junctions provide similar functions in all multicellular organisms, it was not known what proteins invertebrates used for this purpose until the late 1990s. While the

connexin Connexins (Cx)TC# 1.A.24, or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, forms gap junctions in invertebrates. Eac ...

family of gap junction proteins was well-characterized in

vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

, no homologues were found in non-chordates. Innexins or related proteins are widespread among

Eumetazoa Eumetazoa (), also known as Epitheliozoa or Histozoa, is a proposed basal animal subkingdom as a sister group of Porifera (sponges). The basal eumetazoan clades are the Ctenophora and the ParaHoxozoa. Placozoa is now also seen as a eumetazoan ...

, with the exception of

echinoderm An echinoderm () is any animal of the phylum Echinodermata (), which includes starfish, brittle stars, sea urchins, sand dollars and sea cucumbers, as well as the sessile sea lilies or "stone lilies". While bilaterally symmetrical as ...

Discovery

Gap junction proteins with no

sequence homology Sequence homology is the homology (biology), biological homology between DNA sequence, DNA, RNA sequence, RNA, or Protein primary structure, protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments ...

to connexins were initially identified in fruit flies. It was suggested that these proteins are specific invertebrate gap junctions, and they were thus named "innexins" (invertebrate analog of connexins). They were later identified in diverse invertebrates. Invertebrate genomes may contain more than a dozen innexin genes. Once the human genome was sequenced, innexin homologues were identified in humans and then in other vertebrates, indicating their ubiquitous distribution in the animal kingdom. These homologues were called " pannexins" (from the Greek ''pan'' - all, throughout, and Latin ''nexus'' - connection, bond). However, increasing evidence suggests that pannexins do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins.

Structure

Innexins have four transmembrane segments (TMSs) and, like the vertebrate

gap junction protein, innexin subunits together form a channel (an "innexon") in the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

of the cell. Two innexons in apposed plasma membranes can form a gap junction. Innexons are made from eight subunits, instead of the six subunits of connexons. Structurally, innexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 intracellular loop, along with intracellular N- and C-terminal tails. Despite this shared topology, the protein families do not share enough sequence similarity to confidently infer common ancestry. Pannexins are similar to innexins and are usually considered a sub-group, but they do not participate in the formation of gap junctions and the channels have seven subunits. Vinnexins, viral homologues of innexins, were identified in polydnaviruses that occur in obligate symbiotic associations with parasitoid wasps. It was suggested that vinnexins may function to alter gap junction proteins in infected host cells, possibly modifying cell-cell communication during encapsulation responses in parasitized insects.

Function

Innexins form gap junctions found in invertebrates. They also form non-junctional membrane channels with properties similar to those of pannexons. N-terminal- elongated innexins can act as a plug to manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly to apoptotic

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

from the intracellular to the extracellular compartment. The vertebrate homolog pannexin do not form gap junctions. They only form the hemichannel "pannexons". These hemichannels can be present in plasma, ER and Golgi membranes. They transport Ca²⁺, ATP,

inositol triphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

and other small molecules and can form hemichannels with greater ease than connexin subunits.

Transport reaction

The transport reactions catalyzed by innexin gap junctions is: :Small molecules (cell 1 cytoplasm) ⇌ small molecules (cell 2 cytoplasm) Or for hemichannels: :Small molecules (cell cytoplasm) ⇌ small molecules (out)

Examples

* ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

'' ** ''unc-7'' ** ''unc-9'' ** ''inx-3'' * ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

'' ** Inx2 ** Inx3 ** Inx4 (zero population growth, zpg) ** Ogre ** shaking-B * ''

Hirudo medicinalis ''Hirudo medicinalis'', or the European medicinal leech, is one of several species of leeches used as medicinal leeches. Other species of ''Hirudo'' sometimes also used as medicinal leeches include ''Hirudo orientalis, H. orientalis'', ''Hirudo ...

'' ** Hm-inx1 ** Hm-inx2 ** Hm-inx3 ** Hm-inx6

References

External links

Description at wustl.edu
{{CCBYSASource, sourcepath= http://tcdb.org/search/result.php?tc=1.a.25, sourcearticle= 1.A.25 The Gap Junction-forming Innexin (Innexin) Family , revision=699838558 Protein families Membrane proteins Transmembrane proteins Transmembrane transporters Transport proteins Integral membrane proteins