Connexon

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Connexon
Connexon and connexin structure
Details
Identifiers
Latinconnexona
THH1.00.01.1.02025
Anatomical terminology

In

intracellular signaling.[2] In still other cells connexons have been shown to occur in mitochondrial membranes and appear to play a role in heart ischaemia.[3]

Connexons made of the same type of connexins are considered

heteromeric.[4]

Structure

Assembly

The assembly of connexins destined for gap junction plaques begins with synthesis of connexins within the cell and ends with the formation of gap junction channel plaques on the cell membrane. The connexin subunit proteins that make up connexons are synthesized on the membranes of the cell's endoplasmic reticulum. These subunits are then oligomerized, or combined with other smaller parts, into connexons in the golgi apparatus.[5] The connexons are then delivered to their proper location on the plasma membrane.[6] Connexons then dock with compatible connexons from the neighboring cell to form gap junction channel plaques.[5] A large part of this process is mediated by phosphorylation of different enzymes and proteins, allowing and preventing interaction between certain proteins.[5] The connexons forming channels to the cell exterior or in mitochondria will require a somewhat altered path of assembly.

General

Connexons contribute to the formation of gap junctions, and are an essential component of the electric synapses in neural pathways.

C terminals reside intracellularly. Connexin types can be further differentiated by using their predicted molecular weight (ex: Connexin 43 is Cx 43 due to its molecular weight of 43 kDa). Connexons will form the gap junction by docking a hemi-channel to another hemi-channel in an adjacent cell membrane.[2] During this phase, the formation of intercellular channels spanning both of the plasma membranes occurs. Subsequently, this process leads to a better understanding of how electric synapses are facilitated between neurons.[2]
Early research identified connexons through their presence in gap junctions. Since then, connexons have been increasingly detected forming channels in single membranes considerably broadening their functionality in cells and tissues.[7]

Degradation

Connexon structure is degraded by its removal from the plasma membrane. Connexons will be internalized by the cell itself as a double membrane channel structure (due to the docking of hemi-channels).

ubiquitination signals degradation within the cell.[5]

Cellular functions

Properties

The properties of individual connexin proteins determine the overall properties of the whole connexon channel. The

nucleotides, ions and glucose.[2] Channels are also voltage sensitive. The connexon channels have voltage-dependent gates that open or close depending on the difference in voltage between the interiors of the two cells.[2] Gates can also show voltage sensitivity depending on the difference in voltage from the interior and exterior of the cell (i.e. membrane potential).[2]

Modulation

Communication between gap-junctions can be modulated/regulated in many ways. The main types of modulation are:

Overall functions

Connexons play an imperative role in behavior and neurophysiology. Many of the details surrounding their pathological functions remain unknown as research has only begun recently. In the central nervous system (CNS), connexons play a major role in conditions such as

purinergic signaling (form of extracellular signaling mediated by purine nucleotides and nucleosides such as adenosine and ATP) and permeability to ATP.[1] Other important roles of connexons are glucose sensing and signal transduction. Connexons cause changes in extracellular glucose concentrations affecting feeding/satiety behavior, sleep-wake cycles, and energy use.[1] Further studies indicate that there is an increase in glucose uptake mediated by connexons (whose mechanism is still not fully understood) and under times of high stress and inflammation.[1] Recent research also indicates that connexons may affect synaptic plasticity
, learning, memory, vision, and sensorimotor gating.

Related diseases

Some of the diseases associated with connexons are cardiovascular disease and diabetes, which is the inability of the body to produce insulin for glucose uptake by cells and degradation in the smaller units of connexons, called connexins, possibly leading to the onset of heart disease. Cardiovascular disease and diabetes, type I and II, affects similar locations within cells of the heart and pancreas. This location is the gap junction, where connexons facilitate rapid cell-to-cell interactions via electrical transmissions. Gap junctions are often present at nerve endings such as in cardiac muscle and are important in maintaining homeostasis in the liver and proper function of the kidneys. The gap junction itself is a structure that is a specialized transmembrane protein formed by a connexon hemichannel.[8] Cardiovascular disease and possibly type I and II diabetes, are each associated with a major protein connexin that makes up the gap junction.

In cardiovascular disease, Cx43 (connexin 43), a subunit of a connexon, is a general protein of the gap junction stimulating cardio

arrhythmias.[8]

Connexons are also associated with both

G-protein coupled receptors, tyrosine-kinase receptors, and cell-to-cell contact.[4] The gap junctions in these tissues supported by endocrine signaling arbitrate intracellular signals between cells and larger organ systems by connecting adjacent cells to each other in a tight fit. The Tight fit of the gap junction is such that cells in the tissue can communicate more efficiently and maintain homeostasis. Thus the purpose of the gap junction is to regulate the passage of ions, nutrients, metabolites, second messengers, and small biological molecules.[4] In diabetes the subsequent loss or degradation of Cx36 substantially inhibits insulin production in the pancreas and glucose in the liver which is vital for the production of energy for the entire body. A deficiency of Cx36 adversely affects the ability of the gap junction to operate within these tissues leading a reduction in function and possible disease. Similar symptoms associated with the loss or degradation of the gap junction have been observed in type II diabetes, however, the function of Cx36 in Type 1 and type II diabetes in humans is still unknown. Additionally, the Cx36 connexin is coded for by GJD2 gene, which has a predisposition on the gene locus for type II diabetes, and diabetic syndrome.[4]

References

  1. ^
    PMID 25408635
    .
  2. ^
    S2CID 176666
    .
  3. PMID 18006437
    .
  4. ^
    PMID 22536530
    .
  5. ^
    PMID 23455769
    .
  6. PMID 12149451
    .
  7. PMID 23088917
    .
  8. ^
    PMID 20038808
    .
  9. ^
    PMID 19966054
    .

Further reading
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