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PLEC1
Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues. Structure Plectin can exist in cells as several alternatively-spliced isoforms, all around 500 kDa and >4000 amino acids. The structure of plectin is thought to be a dimer consisting of a central coiled coil of alpha helices connecting two large globular domains (one at each terminus). These globular domains are responsible for connecting plectin to its various cytoskeletal targets. The carboxy-terminal domain is made of 6 highly homologous repeating regions. The subdomain between regions five ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Skeletal Muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle tissue, and are often known as muscle fibers. The muscle tissue of a skeletal muscle is striated – having a striped appearance due to the arrangement of the sarcomeres. Skeletal muscles are voluntary muscles under the control of the somatic nervous system. The other types of muscle are cardiac muscle which is also striated and smooth muscle which is non-striated; both of these types of muscle tissue are classified as involuntary, or, under the control of the autonomic nervous system. A skeletal muscle contains multiple muscle fascicle, fascicles – bundles of muscle fibers. Each individual fiber, and each muscle is surrounded by a type of connective tissue layer of fascia. Muscle fibers are formed from the cell fusion, fusion of ...
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Hemidesmosomes
Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion. Structure Hemidesmosomes can be categorized into two types based on their protein constituents. Type 1 hemidesmosomes are found in stratified and pseudo-stratified epithelium. Type 1 hemidesmosomes have five main elements: integrin α6 β4, plectin in its i ...
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Desmosomes
A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa, and epithelia. Structure Desmosomes are composed of desmosome-intermediate filament complexes (DIFC), which is a network of cadherin proteins, linker proteins and intermediate filaments. The DIFCs can be broken into three regions: the extracellular core region, or desmoglea, the outer dense plaque, or ODP, and the inner dense plaque, or IDP. The extracellular core region, approximately 34 nm in length, contains desmoglein and desmocollin, which are in the cadherin famil ...
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Desmin
Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture. Structure Desmin is a 53.5 kD protein composed of 470 amino acids, encoded by the human ''DES'' gene located on the long arm of chromosome 2. There are three major domains to the desmin protein: a conserved alpha helix rod, a variable non alpha helix head, and a carboxy-terminal tail. Desmin, as all intermediate filaments, shows no polarity when assembled. The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it. The rod domain connects to the head domain. The head domain 84 amino acids with many arginine, serine, and aromatic residues is important in filament assembly and dimer-dimer interactions. The tail domain is responsible for the integration of filaments and interaction ...
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Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows visualization of the distribution of the target molecule through the sample. The specific region an antibody recognizes on an antigen is called an epitope. There have been efforts in epitope mapping since many antibodies can bind the same epitope and levels of binding between antibodies that recognize the same epitope can vary. Additionally, the binding of the fluorophore to the antibody itself cannot interfere with the immunological specificity of the antibody or the binding capacity of its antigen. Immunofluorescence is a widely used example of immunostaining (using antibodies to stain proteins) and is a specific example of immunohistochemistry (the use of the antibody-antigen rel ...
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Immunoblotting
The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detecting the proteins, this technique is also utilized to visualize, distinguish, and quantify the different proteins in a complicated protein combination. Western blot technique uses three elements to achieve its task of separating a specific protein from a complex: separation by size, transfer of protein to a solid support, and marking target protein using a primary and secondary antibody to visualize. A synthetic or animal-derived antibody (known as the primary antibody) is created that recognizes and binds to a specific target protein. The electrophoresis membrane is washed in a solution containing the primary antibody, before excess antibody is washed off. A secondary antibody is added which recognizes and binds to the primary antibody ...
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Intercalated Disc
Intercalated discs or lines of Eberth are microscopic identifying features of cardiac muscle. Cardiac muscle consists of individual heart muscle cells (cardiomyocytes) connected by intercalated discs to work as a single functional syncytium. By contrast, skeletal muscle consists of multinucleated muscle fibers and exhibits no intercalated discs. Intercalated discs support synchronized contraction of cardiac tissue. They occur at the Z line of the sarcomere and can be visualized easily when observing a longitudinal section of the tissue. Structure Intercalated discs are complex structures that connect adjacent cardiac muscle cells. The three types of cell junction recognised as making up an intercalated disc are desmosomes, fascia adherens junctions, and gap junctions. * Fascia adherens are anchoring sites for actin, and connect to the closest sarcomere. * Desmosomes prevent separation during contraction by binding intermediate filaments, anchoring the cell membrane to the interm ...
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Keratinocyte
Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''stratum basale'') of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, Dehydration, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually be shed off, which happens every 40 to 56 days in humans. Function The primary function of keratinocytes is the formation of a barrier against environmental damage by heat, UV radiation, Dehydration, wat ...
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Knockout Mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. Mice are currently the laboratory animal species most closely related to humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, for whi ...
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ITGB4
Integrin, beta 4 (ITGB4) also known as CD104 (Cluster of Differentiation 104), is a human gene. Function Integrins are heterodimers composed of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Interactions ITGB4 has been shown to interact with Collagen, type XVII, alpha 1, EIF6 and Erbin. See al ...
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SPTAN1
Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the ''SPTAN1'' gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain–Barré syndrome and infantile congenital heart disease. Structure Alternate splicing of alpha II-spectrin has been documented and results in multiple transcript variants; specifically, cardiomyocytes have four identified alpha II-spectrin splice variants. As opposed to alpha I-spectrin that is principally found in erythrocytes, alpha II-spectrin is expressed in most tissues. In cardiac tissue, alpha II-spectrin is found in myocytes at Z-discs, costameres, and the sarcolemma membrane, and in cardiac fibroblasts along the surface of ...
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