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Desmocollins are a subfamily of desmosomal
Desmocollins are a subfamily of desmosomal cadherin
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to allow cells to adhere to each other . Cadherins are a class of type-1 transmembrane proteins, ...
s, the transmembrane constituents of desmosome
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 adh ...
s. They are co-expressed with desmoglein
The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another.
Pathology
Desmogleins are targeted in the autoimmune disea ...
s to link adjacent cells by extracellular adhesion. There are seven desmosomal cadherins in humans, three desmocollins and four desmogleins. Desmosomal cadherins allow desmosomes to contribute to the integrity of tissue structure in multicellular living organisms.
Structure
Threeisoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of desmocollin proteins have been identified.
* Desmocollin-1, coded by the DSC1
Desmocollin-1 is a protein that in humans is encoded by the ''DSC1'' gene.
The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family memb ...
gene
* Desmocollin-2, coded by the DSC2
Desmocollin-2 is a protein that in humans is encoded by the ''DSC2'' gene. Desmocollin-2 is a cadherin-type protein that functions to link adjacent cells together in specialized regions known as desmosomes. Desmocollin-2 is widely expressed, and is ...
gene
* Desmocollin-3, coded by the DSC3
Desmocollin-3 is a protein that in humans is encoded by the ''DSC3'' gene.
Gene
The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Alternative splicing results in two transcript var ...
gene
Each desmocollin gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
encodes a pair of proteins: a longer 'a' form and a shorter 'b' form. The 'a' and 'b' forms differ in the length of their C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
tails. The protein pair is generated by alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
.
Desmocollin has four cadherin-like extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
domains, an extracellular anchor domain, and an intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
anchor domain. Additionally, the 'a' form has an intracellular cadherin-like sequence domain, which provides binding site
In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may inclu ...
s for other desmosomal proteins such as plakoglobin
Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the ''JUP'' gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic compone ...
.
Expression
The desmosomal cadherins are expressed in tissue-specific patterns. Desmocollin-2 and desmoglein-2 are found in all desmosome-containing tissues such as colon and cardiac muscle tissues, while other desmosomal cadherins are restricted to stratified epithelial tissues. All seven desmosomal cadherins are expressed inepidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
, but in a differentiation-specific manner. The '2' and '3' isoforms of desmocollin and desmoglein are expressed in the lower epidermal layers, and the '1' proteins and desmoglein-4 are expressed in the upper epidermal layers. Different isoforms are located in the same individual cells, and single desmosomes contain more than one isoform of both desmocollin and desmoglein.
It is unclear why there are multiple desmosomal cadherin isoforms. It is thought that they may have different adhesive properties that are required at different levels in stratified epithelia or that they have specific functions in epithelial differentiation.
Disorders
Desmosomes are involved in cell-cell adhesion, and are particularly important for the integrity of heart and skin tissue. Because of this, desmocollin gene mutations can affect the adhesion of cells that undergo mechanical stress, notablycardiomyocytes
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
and 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 (''str ...
s. Genetic disorders associated with desmocollin gene mutations include Carvajal syndrome
Palmoplantar keratodermas are a heterogeneous group of disorders characterized by abnormal thickening of the stratum corneum of the palms and soles.
Autosomal recessive, dominant, X-linked, and acquired forms have all been described.
Types
Cli ...
, striate palmoplantar keratoderma
Palmoplantar keratodermas are a heterogeneous group of disorders characterized by abnormal thickening of the stratum corneum of the palms and soles.
Autosomal recessive, dominant, X-linked, and acquired forms have all been described.
Types
Cli ...
, Naxos disease
__notoc__
Naxos disease (also known as "diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy" or "diffuse palmoplantar keratoderma with woolly hair and arrhythmogenic right ventricular cardiomyopathy", first desc ...
, and arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), most commonly is an inherited heart disease.
ACM is caused by genetic defects of the parts of hea ...
.
There is also evidence that autoimmunity
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
against desmosomal cadherins contributes to cardiac inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
associated with arrhythmogenic right ventricular cardiomyopathy, and that anti-desmosomal cadherin antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
may represent new therapeutic targets.
See also
*Desmoglein
The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another.
Pathology
Desmogleins are targeted in the autoimmune disea ...
, a subfamily of desmosomal cadherins
* Armadillo
Armadillos (meaning "little armored ones" in Spanish) are New World placental mammals in the order Cingulata. The Chlamyphoridae and Dasypodidae are the only surviving families in the order, which is part of the superorder Xenarthra, along wi ...
protein family, instrumental in the cytoplasmic anchoring of cadherins
** Plakoglobin
Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the ''JUP'' gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic compone ...
** Plakophilin Plakophilin are proteins of the cytoskeleton. They are involved in regulating the adhesive activity of cadherin.
The three types of plakophilin proteins found in humans are PKP1, PKP2, and PKP3; all exhibiting dual localization in the nucleus as w ...
* Plakin A plakin is a protein that associates with junctional complexes and the cytoskeleton.
Types include desmoplakin, envoplakin, periplakin, plectin, bullous pemphigoid antigen 1, corneodesmosin
Corneodesmosin is a protein that in humans is encoded ...
protein family, associates intercellular bridges to cytoskeleton
** Desmoplakin
Desmoplakin is a protein in humans that is encoded by the ''DSP'' gene. Desmoplakin is a critical component of desmosome structures in cardiac muscle and epidermal cells, which function to maintain the structural integrity at adjacent cell contact ...
*List of target antigens in pemphigus
Circulating auto-antibodies in the human body can target normal parts of the skin leading to disease. This is a list of antigens in the skin that may become targets of circulating auto-antibodies leading to the various types of pemphigus.
...
*List of conditions caused by problems with junctional proteins
Mutations of proteins that hold the cells of the skin together can cause disease. Autoantibodies against proteins that hold the cells of the skin together can also cause disease.
See also
* List of keratins expressed in the human integumen ...
References
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