Connexon

Connexon and connexin structure

Assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells.

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Connexon and connexin structure

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Connexin

Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions.

Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions.

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Life cycle and protein associations of connexins. Connexins are synthesized on ER-bound ribosomes and inserted into the ER cotranslationally. This is followed by oligomerization between the ER and trans-Golgi network (depending on the connexin type) into connexons, which are then delivered to the membrane via the actin or microtubule networks. Connexons may also be delivered to the plasma membrane by direct transfer from the rough ER. Upon insertion into the membrane, connexons may remain as hemichannels or they dock with compatible connexons on adjacent cells to form gap junctions. Newly delivered connexons are added to the periphery of pre-formed gap junctions, while the central "older" gap junction fragment are degraded by internalization of a double-membrane structure called an annular junction into one of the two cells, where subsequent lysosomal or proteasomal degradation occurs, or in some cases the connexons are recycled to the membrane (indicated by dashed arrow). During their life cycle, connexins associate with different proteins, including (1) cytoskeletal components as microtubules, actin, and actin-binding proteins α-spectrin and drebrin, (2) junctional molecules including adherens junction components such as cadherins, α-catenin, and β-catenin, as well as tight junction components such as ZO-1 and ZO-2, (3) enzymes such as kinases and phosphatases which regulate the assembly, function, and degradation, and (4) other proteins such as caveolin. This image was prepared by Hanaa Hariri for Dbouk et al., 2009.

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.

Vertebrate gap junction

Gap junction

Gap junctions are specialized intercellular connections between a multitude of animal cell-types.

Gap junctions are specialized intercellular connections between a multitude of animal cell-types.

Vertebrate gap junction
Light microscope images do not allow us to see connexons themselves but do let us see the fluorescing dye injected into one cell moving into neighboring cells when gap junctions are known to be present
Annular gap junction cross section in TEM thin section. Gap junctions are usually linear rather than annular in TEM thin sections. It is thought that annular gap junctions result from engulfment by one of the two cells of the membrane plaque to form a vesicle within the cell. This example shows three layers to the junction structure. The membrane from each cell is the dark line with the whiter narrow gap between the two darkly stained membranes. In such electron micrographs there may appear to be up to 7 layers. Two lipid mono-layers in each membrane can stain as 3 layers plus one layer from the gap between them, similar to two stacked bread sandwiches with space between them

One gap junction channel is composed of two protein hexamers (or hemichannels) called connexons in vertebrates and innexons in invertebrates.

As an action potential (nerve impulse) travels down an axon there is a change in electric polarity across the membrane of the axon. In response to a signal from another neuron, sodium- (Na+) and potassium- (K+) gated ion channels open and close as the membrane reaches its threshold potential. Na+ channels open at the beginning of the action potential, and Na+ moves into the axon, causing depolarization. Repolarization occurs when the K+ channels open and K+ moves out of the axon, creating a change in electric polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the axon terminal where it signals other neurons.

Action potential

Action potential occurs when the membrane potential of a specific cell location rapidly rises and falls.

Action potential occurs when the membrane potential of a specific cell location rapidly rises and falls.

As an action potential (nerve impulse) travels down an axon there is a change in electric polarity across the membrane of the axon. In response to a signal from another neuron, sodium- (Na+) and potassium- (K+) gated ion channels open and close as the membrane reaches its threshold potential. Na+ channels open at the beginning of the action potential, and Na+ moves into the axon, causing depolarization. Repolarization occurs when the K+ channels open and K+ moves out of the axon, creating a change in electric polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the axon terminal where it signals other neurons.
Shape of a typical action potential. The membrane potential remains near a baseline level until at some point in time, it abruptly spikes upward and then rapidly falls.
Approximate plot of a typical action potential shows its various phases as the action potential passes a point on a cell membrane. The membrane potential starts out at approximately −70 mV at time zero. A stimulus is applied at time = 1 ms, which raises the membrane potential above −55 mV (the threshold potential). After the stimulus is applied, the membrane potential rapidly rises to a peak potential of +40 mV at time = 2 ms. Just as quickly, the potential then drops and overshoots to −90 mV at time = 3 ms, and finally the resting potential of −70 mV is reestablished at time = 5 ms.
Action potential propagation along an axon
Ion movement during an action potential.
Key: a) Sodium (Na+) ion. b) Potassium (K+) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump. In the stages of an action potential, the permeability of the membrane of the neuron changes. At the resting state (1), sodium and potassium ions have limited ability to pass through the membrane, and the neuron has a net negative charge inside. Once the action potential is triggered, the depolarization (2) of the neuron activates sodium channels, allowing sodium ions to pass through the cell membrane into the cell, resulting in a net positive charge in the neuron relative to the extracellular fluid. After the action potential peak is reached, the neuron begins repolarization (3), where the sodium channels close and potassium channels open, allowing potassium ions to cross the membrane into the extracellular fluid, returning the membrane potential to a negative value. Finally, there is a refractory period (4), during which the voltage-dependent ion channels are inactivated while the Na+ and K+ ions return to their resting state distributions across the membrane (1), and the neuron is ready to repeat the process for the next action potential.
When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of neurotransmitter molecules that open ion channels in the post-synaptic neuron (bottom). The combined excitatory and inhibitory postsynaptic potentials of such inputs can begin a new action potential in the post-synaptic neuron.
In pacemaker potentials, the cell spontaneously depolarizes (straight line with upward slope) until it fires an action potential.
In saltatory conduction, an action potential at one node of Ranvier causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node.
Comparison of the conduction velocities of myelinated and unmyelinated axons in the cat. The conduction velocity v of myelinated neurons varies roughly linearly with axon diameter d (that is, v ∝ d), whereas the speed of unmyelinated neurons varies roughly as the square root (v ∝√d). The red and blue curves are fits of experimental data, whereas the dotted lines are their theoretical extrapolations.
Cable theory's simplified view of a neuronal fiber. The connected RC circuits correspond to adjacent segments of a passive neurite. The extracellular resistances re (the counterparts of the intracellular resistances ri) are not shown, since they are usually negligibly small; the extracellular medium may be assumed to have the same voltage everywhere.
Electrical synapses between excitable cells allow ions to pass directly from one cell to another, and are much faster than chemical synapses.
Phases of a cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive calcium channels.
Giant axons of the longfin inshore squid (Doryteuthis pealeii) were crucial for scientists to understand the action potential.
As revealed by a patch clamp electrode, an ion channel has two states: open (high conductance) and closed (low conductance).
Tetrodotoxin is a lethal toxin found in pufferfish that inhibits the voltage-sensitive sodium channel, halting action potentials.
Image of two Purkinje cells (labeled as A) drawn by Santiago Ramón y Cajal in 1899. Large trees of dendrites feed into the soma, from which a single axon emerges and moves generally downwards with a few branch points. The smaller cells labeled B are granule cells.
Ribbon diagram of the sodium–potassium pump in its E2-Pi state. The estimated boundaries of the lipid bilayer are shown as blue (intracellular) and red (extracellular) planes.
Equivalent electrical circuit for the Hodgkin–Huxley model of the action potential. Im and Vm represent the current through, and the voltage across, a small patch of membrane, respectively. The Cm represents the capacitance of the membrane patch, whereas the four g's represent the conductances of four types of ions. The two conductances on the left, for potassium (K) and sodium (Na), are shown with arrows to indicate that they can vary with the applied voltage, corresponding to the voltage-sensitive ion channels. The two conductances on the right help determine the resting membrane potential.

When an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as connexons.

Schematic of cell adhesion

Cell adhesion

Process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface.

Process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface.

Schematic of cell adhesion
Overview diagram of different types of cell junctions present in epithelial cells, including cell–cell junctions and cell–matrix junctions.
Adheren junction showing homophilic binding between cadherins and how catenin links it to actin filaments
Gap junctions showing connexons and connexins
Hemidesmosomes diagram showing interaction between integrins and laminin, including how integrins are linked to keratin intermediate filaments

Gap junctions are composed of channels called connexons, which consist of transmembrane proteins called connexins clustered in groups of six.

Kinesin is a protein complex functioning as a molecular biological machine. It uses protein domain dynamics on nanoscales

Protein complex

Group of two or more associated polypeptide chains.

Group of two or more associated polypeptide chains.

Kinesin is a protein complex functioning as a molecular biological machine. It uses protein domain dynamics on nanoscales
The Bacillus amyloliquefaciens ribonuclease barnase (colored) and its inhibitor (blue) in a complex
Essential proteins in yeast complexes occur much less randomly than expected by chance. Modified after Ryan et al. 2013

Connexons are an example of a homomultimeric protein composed of six identical connexins.

Some examples of cell junctions

Cell junction

Cell junctions (or intercellular bridges ) 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.

Cell junctions (or intercellular bridges ) 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.

Some examples of cell junctions
This image shows a desmosome junction between cells of the epidermal layer of the skin.
The cartoon of epithelium cells connected by tricellular junctions at the regions where three cells meet.

This is possible due to six connexin proteins interacting to form a cylinder with a pore in the centre called a connexon.

Ischemic preconditioning of the heart (B) provides functional recovery of the heart contractile activity at reperfusion

Ischemic preconditioning

Experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types.

Experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types.

Ischemic preconditioning of the heart (B) provides functional recovery of the heart contractile activity at reperfusion

There have been many suggestions to what this might be, including the sarcolemmal ATP-sensitive potassium channel, the mitochondrial ATP-sensitive potassium channel, the mitochondrial permeability transition pore, reactive oxygen species generation, chloride channels, the inward rectifier potassium ion channel, and connexon 43 related channels.

The foot of a person with Charcot–Marie–Tooth disease: The lack of muscle, a high arch, and claw toes are signs of this genetic disease.

Charcot–Marie–Tooth disease

Hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body.

Hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body.

The foot of a person with Charcot–Marie–Tooth disease: The lack of muscle, a high arch, and claw toes are signs of this genetic disease.
Chromosome 17
Denervation atrophy of type II muscle fibers
Ankle-foot orthosis

In CMTX, mutated connexons create non-functional gap junctions that interrupt molecular exchange and signal transport.

A gap junction in a cell membrane

Rotigaptide

Drug under clinical investigation for the treatment of cardiac arrhythmias – specifically atrial fibrillation.

Drug under clinical investigation for the treatment of cardiac arrhythmias – specifically atrial fibrillation.

A gap junction in a cell membrane

Each gap junction is composed of a series of connexons in close proximity to each other.

Main glands of the endocrine system

Endocrine system

Messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs.

Messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs.

Main glands of the endocrine system
Female endocrine system
Male endocrine system

It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as connexons.