Mucin
Mucins (Latin mucus " slime " ) are the structure-giving component of the mucus of organisms. These protective substances may be ( eponymous for slime molds ) formed by many microorganisms, plants and animals. They can be used externally (for example, in prokaryotes, protozoa, molluscs ) or for protection lining of internal organs on the mucous membranes ( mucosa). Mucins are glycoproteins, ie macromolecules from a central protein chain ( long ) side chains of sugars ( polysaccharides ). The polysaccharides give the mucins a high water binding capacity and protect the central protein from enzymatic degradation ( proteolysis ) or the action of acids ( in the digestive system ). Mucins play a role in the barrier function through the mucous membranes, and adhesion.
Naming and classification
The mucins are functionally divided into two groups: in membrane-bound and secreted mucins in.
Regardless they are in humans under the symbol " MUC " followed by a number of named or numbered (MUC1, MUC2, MUC3A etc.). In 2002, sixteen mucin genes were known in man: MUC1, MUC2, MUC3A, MUC3B, MUC4, MUC5AC, MUC5B, MUC6 -9, MUC11 -13, MUC16 and MUC17. This designation has been criticized because it suggests the existence of a family of genes, while the corresponding sequence homology often missing between the genes of the different mucins.
For MUC1, MUC3A ( isoform 1), MUC3B and MUC4 are transmembrane proteins that contribute with their extracellular domain to the glycocalyx, MUC2, MUC5AC, MUC5B, MUC6 and MUC7 are secreted by the mucous membranes ( " secretory mucins " ) and MUC8 can not clearly fit into one of these categories.
Construction
Mucins are composed of a central protein highly glycosylated, that is, covalently bonded polysaccharides is provided. The polysaccharides typically account for 60-80 percent of the mass mucin. They have a very high molecular mass around 120 × 106 daltons and often carry through sialyl - or sulfate groups a high negative charge. This anionic character and the hydroxyl groups in the polysaccharides allow mucins to bind much water per se, and thus lead to the gel or mucus- like consistency of the mucins. The central protein is rich in the amino acids serine, threonine and proline. It contains all the previously known several mucins tandem repeat domains, which are also the regions of the protein to which the polysaccharides are bound by O-glycosylation of the protein. This tandem -repeat domains distinguish the "real" mucins of mucinähnlichen glycoproteins as GlyCAM1 or MadCAM1 that play a role in adhesion.
The polysaccharide usually starts with an N- acetylgalactosamine, which is covalently linked through the alcohol function of the serine or threonine, that is, through an oxygen atom to the protein backbone, and is composed of about 5-10 monosaccharides per chain. This differs from most other mucins glycoproteins where the N- acetylgalactosamine is connected via an amide group with asparagine. The first and possibly also the second sugar of the oligosaccharide is determined by the structure of the underlying protein. However, other sugars are independent and are probably determined only by the concentrations of the corresponding glycosyltransferases.
It is likely that the individual mucins are disulfide linked to each other, whereby the occurrence of nonlinear Mucinketten be explained with about twenty times the mass of a single mucin.
The ends of the polysaccharides are partially provided with sulfate groups or O -acetylated sialic acid groups to impede degradation of mucins by bacteria.
Function
In the animal ( and human) body are mucins of the mucous membranes ( eg eyes, bronchi, mouth, nose, stomach, intestines ) to protect against chemical and mechanical influences of mucous glands secreted (retired ). They are formed, for example, in the stomach of subsidiary cells. These secrete mucins loaded with bicarbonate ( Bikarbonatbatterien belonging to the Bikarbonatsystem of the gastrointestinal tract ) scavenge or neutralize hydrochloric acid ( gastric mucosal barrier ). Other resources in: cartilage, tendons, skin, serum, vitreous and as nubecula in urine.
MUC1, MUC2, MUC3, and MUC4 are mainly in the colon (colon ) occurring mucins. The largest portion of the secreted mucins MUC2 has. In the small intestine is MUC3 mainly secreted mucin.
History
Mucus or mucin were from Clamer Herman Hoff Bauer ( 1734) described for the first time.
Until the 1970s the term was used for the main mucin glycoprotein component of mucus secreted, which was, however, poorly characterized. At this time, the high part of the negatively charged carbohydrates mainly (more than 50 mass percent) and the high content of the amino acids threonine and serine in the protein of mucins was known. In the 1980s, however, showed through the use of advanced spectroscopic methods ( newer forms of mass spectrometry and nuclear magnetic resonance spectroscopy ) that mucins have a much more complex glycosylation, as previously thought. Around the same time epitopes were found on genes for Mucinexpression, which have been associated with tumors. In 1990, the DNA sequences of the first four genes for mucins were decrypted.
Use
In medicine, mucins are used as components of artificial saliva therapeutic.
An increased production of mucins is observed in many adenocarcinomas such as cancer, stomach cancer, lung cancer, prostate cancer or breast cancer. Also in lung diseases such as asthma, bronchitis or chronic obstructive pulmonary disease (COPD) Mucins are overexpressed. Especially the two mucins MUC1 and MUC4 have been and are therefore intensively studied for their pathological functioning. These mucins are potential tumor markers as well as targets for new therapies for diagnosis.