Innexin

Last updated
Innexin
Identifiers
SymbolInnexin
Pfam PF00876
InterPro IPR000990
TCDB 1.A.25
OPM superfamily 194
OPM protein 5h1r
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Innexins are transmembrane proteins that form gap junctions in invertebrates. Gap junctions are composed of membrane proteins that form a channel permeable to ions and small molecules connecting the cytoplasm 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 family of gap junction proteins was well-characterized in vertebrates, no homologues were found in non-chordates.

Contents

Innexins or related proteins are widespread among Eumetazoa, with the exception of echinoderms. [1]

Discovery

Gap junction proteins with no sequence homology 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). [2] 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). [3] [4] However, increasing evidence suggests that pannexins do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins. [5]

Structure

Innexins have four transmembrane segments (TMSs) and, like the vertebrate connexin gap junction protein, innexin subunits together form a channel (an "innexon") in the plasma membrane of the cell. [6] Two innexons in apposed plasma membranes can form a gap junction. Innexons are made from eight subunits, instead of the six subunits of connexons. [7] 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. [8] [9]

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. [10] [11] [12]

Function

Innexins form gap junctions found in invertebrates. They also form non-junctional membrane channels with properties similar to those of pannexons. [13] 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 from the intracellular to the extracellular compartment. [14]

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 and other small molecules and can form hemichannels with greater ease than connexin subunits. [15]

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

See also

Related Research Articles

<span class="mw-page-title-main">Gap junction</span> Cell-cell junction composed of innexins or connexins,

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 regulated gate between cells.

<span class="mw-page-title-main">Cell adhesion</span> Process of cell attachment

Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.

<span class="mw-page-title-main">Connexon</span> Protein hexamer that forms the pore of gap junctions between cells

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. 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 still other cells connexons have been shown to occur in mitochondrial membranes and appear to play a role in heart ischaemia.

<span class="mw-page-title-main">Connexin</span> Group of proteins which form the intermembrane channels of gap junctions

Connexins (Cx), 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. Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits, each of which consist of four transmembrane segments. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. Connexins also have non-channel dependant functions relating to cytoskeleton and cell migration. For these reasons, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.

Cell junctions or junctional complexes, are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.

<span class="mw-page-title-main">Juxtacrine signalling</span> Contact-based cell-cell signalling

In biology, juxtacrine signalling is a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires close contact. In this type of signalling, a ligand on one surface binds to a receptor on another adjacent surface. Hence, this stands in contrast to releasing a signaling molecule by diffusion into extracellular space, the use of long-range conduits like membrane nanotubes and cytonemes or the use of extracellular vesicles like exosomes or microvesicles. There are three types of juxtacrine signaling:

  1. A membrane-bound ligand and a membrane protein of two adjacent cells interact.
  2. A communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules.
  3. An extracellular matrix glycoprotein and a membrane protein interact.
<span class="mw-page-title-main">Pannexin</span>

Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments.

Membrane channels are a family of biological membrane proteins which allow the passive movement of ions, water (aquaporins) or other solutes to passively pass through the membrane down their electrochemical gradient. They are studied using a range of channelomics experimental and mathematical techniques. Insights have suggested endocannabinoids (eCBs) as molecules that can regulate the opening of these channels during diverse conditions.

<span class="mw-page-title-main">GJB1</span> Protein-coding gene in the species Homo sapiens

Gap junction beta-1 protein (GJB1), also known as connexin 32 (Cx32) is a transmembrane protein that in humans is encoded by the GJB1 gene. Gap junction beta-1 protein is a member of the gap junction connexin family of proteins that regulates and controls the transfer of communication signals across cell membranes, primarily in the liver and peripheral nervous system.

<span class="mw-page-title-main">GJB6</span> Protein-coding gene in the species Homo sapiens

Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the GJB6 gene. Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear. Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness. Mutations in this gene are associated with Clouston syndrome.

<span class="mw-page-title-main">GJA4</span> Protein-coding gene in the species Homo sapiens

Gap junction alpha-4 protein, also known as Connexin-37 or Cx37, is a protein that in humans is encoded by the GJA4 gene. This protein, like other Connexin proteins, forms connections between cells known as gap junctions. Connexin 37 can be found in many tissues including the ovary, heart, and kidney.

Cell–cell interaction refers to the direct interactions between cell surfaces that play a crucial role in the development and function of multicellular organisms. These interactions allow cells to communicate with each other in response to changes in their microenvironment. This ability to send and receive signals is essential for the survival of the cell. Interactions between cells can be stable such as those made through cell junctions. These junctions are involved in the communication and organization of cells within a particular tissue. Others are transient or temporary such as those between cells of the immune system or the interactions involved in tissue inflammation. These types of intercellular interactions are distinguished from other types such as those between cells and the extracellular matrix. The loss of communication between cells can result in uncontrollable cell growth and cancer.

<span class="mw-page-title-main">GJD4</span> Protein-coding gene in the species Homo sapiens

Gap junction delta-4 protein (GJD4), also known as connexin-40.1 (Cx40.1), is a protein that in humans is encoded by the GJD4 gene.

<span class="mw-page-title-main">GJD3</span> Protein-coding gene in the species Homo sapiens

Gap junction delta-2 (GJD2), also known as connexin-36 (Cx36) or gap junction alpha-9 (GJA9), is a protein that in humans is encoded by the GJD2 gene.

<span class="mw-page-title-main">GJB7</span> Protein-coding gene in the species Homo sapiens

Gap junction beta-7 protein (GJB7), also known as connexin-25 (Cx25), is a protein that in humans is encoded by the GJB7 gene.

<span class="mw-page-title-main">GJA10</span> Protein-coding gene in the species Homo sapiens

Gap junction alpha-10 protein, also known as connexin-62 (Cx62), is a protein that in humans is encoded by the GJA10 gene.

<span class="mw-page-title-main">PANX1</span> Protein-coding gene in the species Homo sapiens

Pannexin 1 is a protein in humans that is encoded by the PANX1 gene.

<span class="mw-page-title-main">Gap junction modulation</span>

Gap junction modulation describes the functional manipulation of gap junctions, specialized channels that allow direct electrical and chemical communication between cells without exporting material from the cytoplasm. Gap junctions play an important regulatory role in various physiological processes including signal propagation in cardiac muscles and tissue homeostasis of the liver. Modulation is required, since gap junctions must respond to their environment, whether through an increased expression or permeability. Impaired or altered modulation can have significant health implications and are associated with the pathogenesis of the liver, heart and intestines.

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 incorporated into the host's cell membranes to alter the way the hosts cells communicate with each other. The altered communication aids the transmission and replication of the virus in complex ways. The communication structure that the vinnexin is involved in is the gap junction and vinnexin forms part of a wider family of proteins that are innexin homologues referred to as pannexins. So far Vinnexins have only been found in Adenovirus and the way they affect the functioning of innexins is being studied in great detail.

<span class="mw-page-title-main">Intercellular communication</span>

"Intercellular communication" refers to the varying ways and structures biological cells use to communicate with each other directly or through their environment. Not all cells use all of the proteins or mechanisms and there are likely to be more yet to be discovered. Components of each type of intercellular communication may be involved in more than one type of communication making attempts at clearly separating the types of communication listed somewhat futile. The sections are loosely compiled from various areas of research rather than by a systematic attempt of classification by functional or structural characteristics.

References

  1. ↑ Hasegawa DK, Turnbull MW (April 2014). "Recent findings in evolution and function of insect innexins". FEBS Letters. 588 (8): 1403–10. doi: 10.1016/j.febslet.2014.03.006 . PMID   24631533. S2CID   25970503.
  2. ↑ Phelan P, Stebbings LA, Baines RA, Bacon JP, Davies JA, Ford C (January 1998). "Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes". Nature. 391 (6663): 181–4. Bibcode:1998Natur.391..181P. doi:10.1038/34426. PMID   9428764. S2CID   205003383.
  3. ↑ Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S (June 2000). "A ubiquitous family of putative gap junction molecules". Current Biology. 10 (13): R473-4. doi: 10.1016/S0960-9822(00)00576-5 . PMID   10898987. S2CID   20001454.
  4. ↑ Kelmanson IV, Shagin DA, Usman N, Matz MV, Lukyanov SA, Panchin YV (December 2002). "Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA". The European Journal of Neuroscience. 16 (12): 2475–6. doi:10.1046/j.1460-9568.2002.02423.x. PMID   12492443. S2CID   41324492.
  5. ↑ Dahl G. & Harris A. 2009. Pannexins or Connexins? Chapter 12. In: A. Harris, D. Locke (eds.), Connexins: A Guide doi : 10.1007/978-1-59745-489-6_12
  6. ↑ Bao L, Samuels S, Locovei S, Macagno ER, Muller KJ, Dahl G (December 2007). "Innexins form two types of channels". FEBS Letters. 581 (29): 5703–8. doi:10.1016/j.febslet.2007.11.030. PMC   2489203 . PMID   18035059.
  7. ↑ Oshima A, Matsuzawa T, Murata K, Tani K, Fujiyoshi Y (March 2016). "Hexadecameric structure of an invertebrate gap junction channel". Journal of Molecular Biology. 428 (6): 1227–1236. doi: 10.1016/j.jmb.2016.02.011 . PMID   26883891.
  8. ↑ Michalski K, Syrjanen JL, Henze E, Kumpf J, Furukawa H, Kawate T (February 2020). "The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition". eLife. 9: e54670. doi: 10.7554/eLife.54670 . PMC   7108861 . PMID   32048993.
  9. ↑ Qu R, Dong L, Zhang J, Yu X, Wang L, Zhu S (March 2020). "Cryo-EM structure of human heptameric Pannexin 1 channel". Cell Research. 30 (5): 446–448. doi:10.1038/s41422-020-0298-5. PMC   7196123 . PMID   32203128.
  10. ↑ Turnbull M, Webb B (2002). Perspectives on polydnavirus origins and evolution. Advances in Virus Research. Vol. 58. pp. 203–54. doi:10.1016/S0065-3527(02)58006-4. ISBN   9780120398584. PMID   12205780.
  11. ↑ Kroemer JA, Webb BA (2004). "Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication". Annual Review of Entomology. 49 (1): 431–56. doi:10.1146/annurev.ento.49.072103.120132. PMID   14651471.
  12. ↑ Marziano N.K.; Hasegawa D.K.; Phelan P.; Turnbull M.W. (October 2011). "Functional Interactions between Polydnavirus and Host Cellular Innexins". Journal of Virology. 85 (19): 10222–9. doi:10.1128/jvi.00691-11. PMC   3196458 . PMID   21813607.
  13. ↑ Bao L, Samuels S, Locovei S, Macagno ER, Muller KJ, Dahl G (December 2007). "Innexins form two types of channels". FEBS Letters. 581 (29): 5703–8. doi:10.1016/j.febslet.2007.11.030. PMC   2489203 . PMID   18035059.
  14. ↑ Chen YB, Xiao W, Li M, Zhang Y, Yang Y, Hu JS, Luo KJ (May 2016). "N-TERMINALLY ELONGATED SpliInx2 AND SpliInx3 REDUCE BACULOVIRUS-TRIGGERED APOPTOSIS VIA HEMICHANNEL CLOSURE". Archives of Insect Biochemistry and Physiology. 92 (1): 24–37. doi:10.1002/arch.21328. PMID   27030553.
  15. ↑ Shestopalov VI, Panchin Y (February 2008). "Pannexins and gap junction protein diversity". Cellular and Molecular Life Sciences. 65 (3): 376–94. doi:10.1007/s00018-007-7200-1. PMID   17982731. S2CID   23181471.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR000990

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