Innexins are

transmembrane proteins A transmembrane protein (TP) 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 frequentl ...

that form

gap junction Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...

s in

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

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 Channel, channels, channeling, etc., may refer to: Geography * Channel (geography), in physical geography, a landform consisting of the outline (banks) of the path of a narrow body of water. Australia * Channel Country, region of outback Austral ...

permeable to ions and small molecules connecting the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

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, form gap junctions in invertebrates. Ea ...

family of gap junction proteins was well-characterized in

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

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

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

, with the exception of

echinoderm An echinoderm () is any member of the phylum Echinodermata (). The adults are recognisable by their (usually five-point) radial symmetry, and include starfish, brittle stars, sea urchins, sand dollars, and sea cucumbers, as well as the sea ...

Discovery

Gap junction proteins with no

sequence homology Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...

to connexins were initially identified in

fruit flies Fruit fly may refer to: Organisms * Drosophilidae, a family of small flies, including: ** ''Drosophila'', the genus of small fruit flies and vinegar flies ** ''Drosophila melanogaster'' or common fruit fly ** ''Drosophila suzukii'' or Asian fruit ...

. 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 "

pannexin Pannexins (from Greek 'παν' — all, and from Latin 'nexus' — connection) are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebr ...

s" (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 (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

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.

Vinnexin Vinnexin is a transmembrane protein whose DNA code is held in a virus genome. When the virus genome is expressed in a cell the vinnexin gene from the virus is made into a functioning protein by the infected cell. The vinnexin protein is then inco ...

s, viral homologues of innexins, were identified in

polydnavirus A polydnavirus (PDV) is a member of the family ''Polydnaviridae'' of insect viruses. There are two genera in the family: '' Bracovirus'' and '' Ichnovirus''. Polydnaviruses form a symbiotic relationship with parasitoid wasps; ( ichnoviruses ( ...

es 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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

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 blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...

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

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic 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" or "pomace fly". Starting with Ch ...

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

Hirudo medicinalis ''Hirudo medicinalis'', 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 '' H. orientalis'', ''H. troctina'', and '' H. ...

'' ** 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