Gap Junction

Gap junctions are collections ( " plaque " or "clusters" ) of two adjacent cells, the cell membranes crossing through cell-cell channels. Connect the cytoplasm of adjacent cells directly. The membranes of the cells are fixed to each other at a distance of only 2 to 4 nanometers, leaving between them but an electron microscopically detectable gap (English: gap) free (as opposed to the tight junctions ). The channels of the gap junction formed from two half- channels ( hemichannels, connexons ), each cell contributes each one. Each connexon consists of protein complexes of (usually ) six membrane-spanning proteins that assemble in a hexagonal arrangement so that stays in the middle between them a pore -free. Two such protein complexes of the adjacent cell membranes of two cells eventually accumulate together so that they together form a channel.

The object of the gap junctions is communication ( exchange of signals ) between adjacent cells. In this case, ions or small molecules by diffusion is transferred directly from one cell to the neighboring cell. This can, for example, serving as a signal transmitter potassium or calcium ions, secondary messengers ( second messengers ) such as cAMP, cGMP, or IP3, or small metabolic products (metabolites ) as his glucose. Depending on the specific construction of the cell the transition duct is more or less selective, it can be obtained by signal generator such as the membrane potential can be controlled. Some types of channels also conduct certain substances selectively on only in one direction.

The channels of gap junctions are composed in various species of two different protein families. Exclusively in the chordates (vertebrates and relatives) they consist of proteins called connexins. For all other tissues animals accomplished this task another family of proteins, which are called innexins. Both are structured functionally similar but have no homologous base sequences, ie they are not closely related to each other. Meanwhile, in vertebrates a family of proteins has been re- discovered the Pannexine, which in their sequence similarity to the larger Innexinen, presumably homologous to them. However Pannexine are extremely rare if very involved in the formation of gap junctions (probably even not at all), they perform other tasks in the cell. Related, membrane-spanning proteins are involved in the formation of tight junctions Claudine and occludin.

In plants, plasmodesmata perform similar tasks, but differ significantly from those of the structure composed of Innexinen and connexin channels.

History of Research

The first indications of the cell coupling came from electrophysiological studies of specific pairs of interacting nerve cells in the spinal cord of the crayfish. The measurement of the electrical coupling of neighboring giant neurons was first described by Fursphan and Potter 1959 performed ( Fursphan and Potter 1959).

Coined the concept of gap junctions by Jean -Paul Revel and Karnovsky Morris 1967, which were the first that narrows in the electron microscopic picture of the distance between two adjacent plasma membranes in the area of ​​gap junctions from 20-30 nm to 2-4 nm, whereby the optical impression of a gap (English: gap) arises in the continuity of adjacent plasma membranes.

Construction

Six connexins ( each with four transmembrane regions ) superimposed to form the so-called connexon (or semi channel) together. A connexon can homomeric ( composition of a type of connexins ) or heteromeric ( from different connexins ) are built. Depending on the composition of the connexons the permeability of the channel may vary.

The half channel connects to an opposite him half-channel of the neighboring cell to form a continuous pore ( intercellular channel, gap junction ). The intercellular channels can be homotypic ( of two identical connexons ) or straight typically be constructed ( from various connexons ), although not all connexons assemble equally well. The pore has a diameter of 1.5 to 2 nm and can therefore pass molecules or ions of a maximum of ≈ 1000 daltons molecular weight. The structure of a gap junction (formerly Nexus ) can be done within a few seconds, when two cells come into contact with each other.

A connexon - subunit has a diameter of 2.5 nm and 7.5 nm in length. It protrudes 0.7 nm and 1.7 nm in the cytosol into the extracellular space.

The connexons in the biomembrane in fields in a regular hexagonal pattern (distance between the center points of channel 8.5 nm ) arranged with a density of from a few up to 28,000 channels per square micron, they form so-called plaques.

Gap junctions are different from other channel systems of the cell:

• You go through two adjacent membranes ( instead of just one ).
• Connect with cytosol cytosol (instead of cytosol with the extracellular space or Organellinnenraum ).
• The connexins are synthesized from two different cells (instead of only one ).
• Usually they are open at rest and close only when certain conditions are met ( see below)

Occurrence and function

Gap junctions occur only at the Eumetazoa. During the embryonic stage gap junctions are widespread, they occur in the adult esp. in the heart muscle, in epithelial and glial cells as well as in the retina.

The general functions of the GJs are

• Direct electrical communication between cells (where different connexins lead to different conductivities )
• Direct chemical communication between cells via second messengers (like IP3, Ca2 ) (where different connexins have different selectivity for small molecules )
• Exchange of molecules between cells to ≈ 1 kDa (with different connexins GJs can form different diameters and different preferences for charged particles have )
• Prevent molecules or charges are lost when exchange in the extracellular space.

Examples of the function of the GJs:

• In weakly perfused tissues (eg eye lens and bones) they serve the Nahtransport of nutrients: Border cells absorb nutrients and pass it over the gap junctions to neighboring cells to the underserved center on.
• In glands such as liver and pancreas help in the secretion.
• In the cardiac muscle and the nervous system they are involved in the fast forward action potentials.
• Gap junctions appear to be also involved in the control of cell growth (for example, during embryonic development ).
• One of the connexin gene has been identified as a tumor suppressor gene.

The pores through a gap junction can be closed very quickly when certain factors occur that suggest harm to the adjacent cell. Thus, the damaged cell is uncoupled from their neighbors, so that the healthy neighboring cells remain unaffected in their cell chemistry. The closing is (that is, at a high proton concentration ) is triggered by a high cytosolic calcium ion concentration or a low cytosolic pH. Both are signs of imminent death of the neighboring cell.

For several years it is known that half- channels formed by all three protein families ( connexins, innexins and Pannexine ) do not have to always be together close to gap junctions. In numerous cells and cell types they fulfill additional functions as a simple membrane channels without coupling to other cells. Probably the Pannexine occur in this form.

Gap junctions as electrical synapses

Gap junctions serve 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 allow rapid and synchronous propagation of action potentials. In the intercalated disks between cardiomyocytes they can cover an area up to one square micron. The conductivity of the gap junctions varies with the composition of different connexins. In neurons, they are not so numerous as to chemical synapses, but they were also found in glial cells, their participation in the neural events on the supply of nerve cells also being explored. The main role of electrical synapses seems the synchronization of groups of neurons to be serving as oscillators and rhythm generator. You may also play a role in epileptic seizures.

Operation of the electrical synapse

The depolarization of the presynaptic cell results in a potential difference between the two cells connected by gap junctions, so that cations flow from the pre-synaptic post-synaptic cell and cell in the direction of anions of the post to pre-synaptic cell.

If the threshold value exceeded at the postsynaptic membrane, here is an action potential, and the signal may almost no time delay ( 10-5 s ) to be forwarded ( for example, makes synchronization of many cells in the heart muscle due to small possible time delay ).

Comparison between electrical and chemical synapse

In addition to the much smaller time delay, electrical synapses of chemical synapses differ in the fact that in these synaptic transmission typically can be done in both directions.

However, gap junctions of some cells can be regulated in its current direction, either dependent on Ca2 or membrane potential - dependent. However, the application of gap junctions in the body also has some disadvantages: No direct excitation transfer to distant cells and esp. can not be used to inhibit another cell excitation. Electrical synapses in the CNS have the mammals of minor importance compared to chemical synapses.

Example uterus

With the beginning of the birth, the muscle of the uterus are equipped with gap junctions that connect the cells to form a syncytium, which can be contracted synchronously.

Swell

• Daisuke Fushiki, Yasuo Hamada, Ryoichi Yoshimura, Yasuhisa Endo (2010): Phylogenetic and bioinformatic analysis of gap junction - related proteins, innexins, pannexins and connexins. Biomedical Research Vol 31 No. 2: 133-142. doi: 10.2220/biomedres.31.133
• Daniel A. Goodenough and David L. Paul (2009): Gap Junctions. Cold Spring Harbor Perspectives in Biology 2009; 1: a002576 doi: 10.1101/cshperspect.a002576
• Gulistan Mese, Gabriele Richard, Thomas W. White ( 2007): Gap Junctions: Basic Structure and Function. 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. 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. 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 connexin, pannexins, innexins: novel roles of " hemi - channels". Pflügers Arch 457 (6): 1207-1226. doi: 10.1007/s00424-008-0591-5