Connexin

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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.

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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Gap junction

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

In vertebrates, gap junction hemichannels are primarily homo- or hetero-hexamers of connexin proteins.

GJA1

Protein that in humans is encoded by the GJA1 gene on chromosome 6.

connexin 43 carboxyl terminal domain
Connexin 43 distribution in the rat myocardium (gap junctions between cardiomyocytes)
Predicted secondary structure and sequence conservation of IRES_Cx43

As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular communication (GJIC) between cells to regulate cell death, proliferation, and differentiation.

Cell adhesion

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.

Connexon

Connexon and connexin structure

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.

Innexin

Innexins are transmembrane proteins that form gap junctions in invertebrates.

Schematic representation of transmembrane proteins: 1) a single transmembrane α-helix (bitopic membrane protein). 2) a polytopic transmembrane α-helical protein. 3) a polytopic transmembrane β-sheet protein. The membrane is represented in light yellow.

While the connexin family of gap junction proteins was well-characterized in vertebrates, no homologues were found in non-chordates.

Pannexin

Pannexins (from Greek 'παν' — all, and from Latin 'nexus' — connection) are a family of vertebrate proteins identified by their homology to the invertebrate innexins.

Schematic diagram of an ion channel. 1 - channel domains (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane.

Intercellular gap junctions in vertebrates, including humans, are formed by the connexin family of proteins.

Voltage clamp

Experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level.

The voltage clamp operates by negative feedback. The membrane potential amplifier measures membrane voltage and sends output to the feedback amplifier; this subtracts the membrane voltage from the command voltage, which it receives from the signal generator. This signal is amplified and output is sent into the axon via the current-passing electrode.
A personal photo of Kenneth Cole, given to Dr. J. Walter Woodbury
Two-electrode voltage clamp

When two cells in which gap junction proteins, typically connexins or innexins, are expressed, either endogenously or via injection of mRNA, a junction channel will form between the cells.

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.

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.

Pericyte

Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body.

Transmission electron micrograph of a microvessel displaying pericytes that are lining the outer surface of endothelial cells that are encircling an erythrocyte (E).
Gap cell junction created between two neighboring cells by connexin.
Image of a solitary fibrous tumour that is most likely a hemangiopericytoma. It surrounds a staghorn-shaped blood vessel, which results from the arrangement of pericytes around the vessel

Important molecules in these intercellular connections include N-cadherin, fibronectin, connexin and various integrins.

Epithelium

One of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue.

Types of epithelium
Summary showing different epithelial cells/tissues and their characteristics.
Forms of secretion in glandular tissue
Different characteristics of glands of the body
Epithelial cell infected with ''Chlamydia pneumoniae
Squamous epithelium 100x
Human cheek cells (Nonkeratinized stratified squamous epithelium) 500x
Histology of female urethra showing transitional epithelium
Histology of sweat gland showing stratified cuboidal epithelium

Gap junctions connect the cytoplasm of two cells and are made up of proteins called connexins (six of which come together to make a connexion).