Gap Junction
| Parent |
| Cell-to-cell contact |
| Subordinate |
|
connexon Pannexon |
| Gene Ontology |
|---|
| QuickGO |
Gap junctions are accumulations ("plaques" or "clusters") of cell-cell channels that cross the cell membranes of two neighboring cells. They connect the cytoplasm of neighboring cells directly to one another. The membranes of the cells are fixed at a distance of only 2 to 4 nanometers from one another, but leave a gap between them that can be recognized by an electron microscope (in contrast to the tight junctions ). The channels of the gap junction are made up of two half-channels (hemichannels, connexons ), of which each cell contributes one. Each connexon consists of protein complexes of (usually) six membrane-spanning proteins, which are arranged in a hexagonal arrangement so that a pore remains free in the middle between them. Two such protein complexes of the neighboring cell membranes of two cells finally accumulate in such a way that they together form a channel.
The task of the gap junctions is the communication (exchange of signals) between neighboring cells. Here are ions or small molecules by diffusion directly transferred from one cell to the neighboring cell. This can e.g. B. potassium or calcium ions serving as signal generators, secondary messenger substances ( second messengers ) such as cAMP , cGMP or IP3 , or small metabolic products ( metabolites ) such as glucose . Depending on the specific structure of the cell channel, the transition is more or less selective. B. the membrane potential can be controlled. Some types of channels also selectively transmit certain substances in only one direction.
The channels of the gap junctions are built up in different animal species by two different protein families . Only in chordates (vertebrates and relatives) do they consist of proteins called connexins . In all other tissue animals , this task is performed by a different family of proteins called innexins . Both are functionally similar, but have no homologous base sequences and are therefore not closely related to one another. In the meantime, a new protein family has been discovered in vertebrates, the pannexins , which are more similar in sequence to the innexins, i.e. are probably homologous to them. However, pannexins are extremely rarely involved in the formation of gap junctions (probably not at all); they perform other tasks in the cell. Other related membrane-spanning proteins are the claudins and occludin involved in the formation of tight junctions .
In plants , the plasmodesmata perform similar tasks, but differ significantly in structure from the channels made up of innexins and connexins.
Research history
The first indications of cell coupling came from electrophysiological studies on specific pairs of interacting nerve cells in the crayfish spinal cord. The measurement of the electrical coupling of these neighboring giant neurons was first carried out by Fursphan and Potter in 1959 (Fursphan and Potter 1959).
The term gap junctions was coined by Jean-Paul Revel and Morris Karnovsky in 1967, who were the first to show that the distance between two adjacent plasma membranes in the area of the gap junctions narrows from 20-30 nm to 2-4 nm in the electron microscope image. whereby the visual impression of a gap (engl .: gap ) is formed in the continuity of adjacent plasma membranes.
construction
Six connexins (each with four transmembrane regions) combine to form the so-called connexon (or half-channel). A connexon can be built up homomerically (composed of one type of connexins) or heteromerically (from different connexins). Depending on the composition of the connexons, the permeability of the channel can vary.
One half-channel each connects to a half-channel opposite to it in the neighboring cell to form a continuous pore (intercellular channel, gap junction). The intercellular canal can be built homotypically (from two identical connexons) or heterotypically (from different connexons), although not all connexons are equally well placed together. The pore has a diameter of 1.5 to 2 nm and therefore allows molecules or ions with a maximum of ≈1000 Dalton relative molecular mass to pass. A gap junction (formerly: nexus) can be set up within a few seconds if two cells come into contact with one another.
A connexon subunit has a diameter of 2.5 nm and is 7.5 nm long. It protrudes 0.7 nm into the cytosol and 1.7 nm into the extracellular space .
The connexons are arranged in fields in the biomembrane in a regular hexagonal pattern (distance between the channel centers 8.5 nm) with a density of a few to 28,000 channels per square micrometer, they form so-called plaques.
Gap junctions differ from other cell channel systems:
- They run through two neighboring membranes (instead of just one).
- They connect cytosol with cytosol (instead of cytosol with extracellular space or organelle interior).
- The connexins are synthesized by two different cells (instead of just one).
- They are usually open when idle and only close when certain conditions occur (see below)
Occurrence and function
Gap junctions only occur with the Eumetazoa . While gap junctions are widespread in the embryonic stage, they occur in the adult v. a. in the heart muscle , in epithelial and glial cells and in the retina .
The general functions of the GJs are
- direct electrical communication between cells (whereby different connexins cause different conductivities)
- direct chemical communication between cells via second messenger (e.g. IP3, Ca 2+ ) (whereby different connexins have different selectivities for small molecules)
- Exchange of molecules up to ≈1 kDa between cells (whereby different connexins can form GJs with different diameters and have different preferences for charged particles)
- prevent molecules or charges from being lost during exchange in the extracellular space.
Examples of the function of the GJs:
- In tissues with poor blood supply (for example the lens of the eye and bones ) they are used for the local transport of nutrients: Edge cells absorb the nutrients and pass them on to their neighboring cells via the gap junctions to the undersupplied center.
- In glands like the liver and pancreas , they aid in secretion .
- In the heart muscle and nervous system , they are involved in the rapid transmission of action potentials .
- Gap junctions also appear to be involved in controlling cell growth (for example, during embryonic development ).
- One of the connexin genes was identified as a tumor suppressor gene.
The pores through a gap junction can be closed very quickly if certain factors occur that indicate damage to the neighboring cell. As a result, the damaged cell is decoupled from its neighbors, so that the healthy neighboring cells remain unaffected in their cell chemistry. Closing is triggered by a high cytosolic calcium ion concentration or a low cytosolic pH value (i.e. with a high proton concentration ). Both are signs of an imminent cell death of the neighboring cell.
It has been known for a number of years that half-channels formed by all three protein families (connexins, innexins and pannexins) do not always have to join together to form gap junctions. In numerous cells and cell types they fulfill additional functions as simple membrane channels without coupling to other cells. The pannexins probably only occur in this form.
Gap junctions as electrical synapses
Gap junctions function in neurons, in the retina and in the heart , but also in invertebrates as voltage-controlled, transmitter-free synapses . They are also known as electrical synapses . They enable a quick and synchronous spread of action potentials . In the shiny strips between the heart muscle cells, they can cover an area of up to a square micrometer. The conductivity of the gap junctions varies with the composition of different connexins. They are not as numerous in neurons as chemical synapses, but they have also been found in glial cells , whose involvement in neuronal processes beyond the supply of the nerve cells is currently being researched. The main task of the electrical synapses seems to be the synchronization of groups of nerve cells that serve as oscillators and rhythm generators. They may also play a role in epileptic seizures.
How the electrical synapse works
The depolarization of the presynaptic cell leads to a potential gradient between the two cells connected by gap junctions, so that cations flow from the presynaptic cell towards the postsynaptic cell and anions from the post- to the presynaptic cell.
If the threshold value on the postsynaptic membrane is exceeded, an action potential follows and the signal can be passed on with practically no time delay (10 −5 s) (makes synchronization of many cells, e.g. in the heart muscle, possible due to the short time delay!).
Comparison between electrical and chemical synapse
In addition to the much smaller time delay, electrical synapses also differ from chemical synapses in that the transmission of excitation i. d. Can usually be done in both directions.
However, gap junctions of some cells can also be regulated in their current direction, either dependent on Ca 2+ or membrane potential-dependent. However, the use of gap junctions in the body also has some disadvantages: A direct transfer of excitation to cells that are far away is not possible, but above all, an excitation cannot be used to inhibit another cell. Electrical synapses are less important in the mammalian CNS than chemical synapses.
| electrical synapse | chemical synapse with direct signal transmission | chemical synapse with indirect signal transmission | |
|---|---|---|---|
| Gap width | 3.5 nm | 30 to 50 nm | 30 to 50 nm |
| Channel proteins | Gap junction channels in the pre- and postsynaptic membrane | postsynaptic, transmitter-controlled ion channels | Receptors of the second messenger system ( G proteins ) |
| Synaptic delay | no | 0.1 to 0.5 ms | more than 10 ms |
| Transmitter | Acetylcholine , gamma-aminobutyric acid (GABA), glycine , glutamate , aspartate | Norepinephrine , dopamine , serotonin , acetylcholine , neuropeptides | |
| Occurrence | Heart muscle, CNS , also in invertebrates | Motor end plates , central and peripheral nervous system | central and peripheral nervous system |
swell
- Revel JP, Karnovsky MJ, Hexagonal array of subunits in intercellular junctions of the mouse heart and liver , J. Cell Biol. 1967; 33: C7-C12.
- Daisuke Fushiki, Yasuo Hamada, Ryoichi Yoshimura, Yasuhisa Endo (2010): Phylogenetic and bioinformatic analysis of gap junction-related proteins, innexins, pannexins and connexins. In: Biomedical Research Vol. 31 no. 2: 133-142. doi : 10.2220 / biomedres.31.133
- Daniel A. Goodenough & David L. Paul (2009): Gap Junctions. Cold Spring Harbor Perspectives in Biology 2009; 1: a002576 doi : 10.1101 / cshperspect.a002576
- Gülistan Mese, Gabriele Richard, Thomas W. White (2007): Gap Junctions: Basic Structure and Function . In: Journal of Investigative Dermatology Volume 127: 2516-2524. doi : 10.1038 / sj.jid.5700770
- Silvia Penuela, Ruchi Gehi, Dale W. Laird (2013): The biochemistry and function of pannexin channels . In: Biochimica et Biophysica Acta 1828: 15-22. doi : 10.1016 / j.bbamem.2012.01.017
- Alberto E. Pereda, Sebastian Curti, Gregory Hoge, Roger Cachope, Carmen E. Flores, John E. Rash (2013): Gap junction-mediated electrical transmission: Regulatory mechanisms and plasticity . In: Biochimica et Biophysica Acta Biomembranes Volume 1828, Issue 1: 134-146 doi : 10.1016 / j.bbamem.2012.05.026
- Eliana Scemes, David C. Spray, Paolo Meda (2009): Connexins, pannexins, innexins: novel roles of “hemi-channels” . In: Pflügers Arch . 457 (6): 1207-1226. doi : 10.1007 / s00424-008-0591-5
