Mucins(/ˈmjuːsɪn/) are a family of highmolecular weight,heavilyglycosylatedproteins (glycoconjugates) produced byepithelialtissues in mostanimals.[1]Mucins' key characteristic is their ability to formgels;therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers.[1]They often take an inhibitory role.[1]Some mucins are associated with controllingmineralization,includingnacreformation inmollusks,[2]calcificationinechinoderms[3]and bone formation in vertebrates.[4]They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especiallyMUC1,is associated with many types of cancer.[5][6]
 | |
| Identifiers | |
|---|---|
| Symbol | Mucin |
| Membranome | 111 |
Although some mucins aremembrane-bound due to the presence of ahydrophobicmembrane-spanning domain that favors retention in theplasma membrane,most mucins aresecretedas principal components ofmucusbymucous membranesor are secreted to become a component ofsaliva.
Genes and proteins
editHuman mucins include genes with theHUGOsymbol MUC 1 through 22. Of these mucins, the following classes have been defined by localization:[7][8][9][10]
- Secreted mucins in humans,with their chromosomal location, repeat size in amino acids (aa), whether they are gel-forming (Y) or not (N), and their tissue expression.[11]
| Mucin | gel | chromosome | repeat size (aa) | tissue expression |
|---|---|---|---|---|
| MUC2 | Y | 11p15.5 | 23 | Jejunum,ileum,colon,endometrium |
| MUC5A | Y | 11p15.5 | 8 | Respiratory tract,stomach,conjunctiva,endocervix,endometrium |
| MUC5B | Y | 11p15.5 | 29 | Respiratory tract,submandibular glands,endocervix |
| MUC6 | Y | 11p15.5 | 169 | Stomach, ileum,gall bladder,endocervix, endometrium |
| MUC19 | Y | 12q12 | 19 | cornealandconjunctivalepithelia;lacrimal gland[12] |
| MUC7 | N | 4q13–q21 | 23 | Sublingualand submandibular glands |
| MUC8 | N | 12q24.3 | 13/41 | Respiratory tract,uterus,endocervix, endometrium |
| MUC9 | N | 1p13 | 15 | Fallopian tubes |
| MUC20 | N | 3 | 19 | kidney(high), moderately inplacenta,lung,prostate,liver,digestive system |
- Membrane-bound (transmembrane) mucins:MUC1,MUC3A,MUC3B,MUC4,MUC12,MUC13,MUC15,MUC16, MUC17,MUC21(formerly C6orf205),MUC22(highly polymorphic[13])
The major secreted airway mucins areMUC5ACandMUC5B,whileMUC2is secreted mostly in the intestine but also in the airway. MUC7 is the major salivary protein.[10]
Protein structure
editMature mammalian mucins are composed of two distinct regions:[7]
- Theamino- andcarboxy-terminal regions are very lightly glycosylated, but rich incysteines.The cysteine residues participate in establishingdisulfidelinkages within and among mucinmonomers.
- A large central region ( "PTS domain" ) formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of theamino acidsareserineorthreonine.This area becomes saturated with hundreds ofO-linkedoligosaccharides.N-linkedoligosaccharidesare also found on mucins, but in less abundance than O-linked sugars.
Evolutionary classification
editThe functional classification does not correspond to an exact evolutionary relationship, which is still incomplete and ongoing.[10]Known-related groups include:
- The gel-forming mucins (2, 5AC, 5B, 6, 19) are related both to each other and tootogelinandvon Willebrand Factor(PTHR11339).[14]Four of these occur in a well-conserved gene cluster (at 11p.15.5 in humans).[15]
- TheEGF-like domaincontaining mucins. These include MUC3(A,B), MUC4, MUC12, MUC13, and MUC17.[16]
- Some EGF-like mucins, plus MUC1 and MUC16, carrySEA domains,a vertebrate invention. It is unclear whether this points to a common origin among these transmembrane mucins.[14]
- MUC21 and MUC22 are related to each other by sharing a C-terminal domain (PF14654). They also occur in a human gene cluster on 6p21.33.
- MUC7 is a recent invention in placental mammals. It started as a copy in thesecretory calcium-binding phosphoprotein(SCPP) gene cluster and rapidly gained PTS repeats.[17]
Function in humans
editMucins have been found to have important functions in defense against bacterial and fungal infections. MUC5B, the predominant mucin in the mouth and female genital tract, has been shown to significantly reduce attachment andbiofilmformation ofStreptococcus mutans,a bacterium with the potential to form cavities.[18]Unusually, MUC5B does not kill the bacteria but rather maintains it in the planktonic (non-biofilm) phase, thus maintaining a diverse and healthy oral microbiome.[18]Similar effects of MUC5B and other mucins have been demonstrated with other pathogens, such asCandida albicans,Helicobacter pylori,and evenHIV.[19][20]In the mouth, mucins can also recruit anti-microbial proteins such asstatherinsandhistatine 1,which further reduces risk of infection.[20]
Eleven mucins are expressed by theeyesurface epithelia,goblet cellsand associated glands, even though most of them are expressed at very low levels. They maintain wetness, lubricate the blink, stabilize thetearfilm, and create a physical barrier to the outside world.[12]
Glycosylation and aggregation
editMucingenesencode mucin monomers that are synthesized as rod-shapedapomucincores that are post-translationally modified by exceptionally abundantglycosylation.
The dense "sugar coating" of mucins gives them considerablewater-holdingcapacity and also makes them resistant toproteolysis,which may be important in maintainingmucosalbarriers.
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 millionDa.Within these aggregates, monomers are linked to one another mostly by non-covalentinteractions, although intermoleculardisulfidebonds may also play a role in this process.
Secretion
editUpon stimulation,MARCKS(myristylated alanine-rich C kinase substrate) protein coordinates the secretion of mucin from mucin-filledvesicleswithin the specialized epithelial cells.[21]Fusion of the vesicles to theplasma membranecauses release of the mucin, which as it exchangesCa2+forNa+expands up to 600 fold. The result is aviscoelasticproduct of interwoven molecules which, combined with other secretions (e.g., from theairway epitheliumand thesubmucosal glandsin therespiratory system), is calledmucus.[22][23]
Clinical significance
editIncreased mucin production occurs in manyadenocarcinomas,including cancers of the pancreas, lung, breast, ovary, colon and other tissues. Mucins are also overexpressed in lung diseases such asasthma,bronchitis,chronic obstructive pulmonary disease(COPD) orcystic fibrosis.[24]Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process.[25][26][27]Mucins are under investigation as possible diagnostic markers for malignancies and other disease processes in which they are most commonly over- or mis-expressed.
Abnormal deposits of mucin are responsible for the non-pitting facialedemaseen in untreatedhypothyroidism.This edema is seen in thepretibialarea as well.[28]
Non-vertebrate mucins
editBeyond the better-studied vertebrate mucins, other animals also express (not necessarily related) proteins with similar properties. These include:
- Drosophilais known to express mucin proteins containing PTS-rich repeats.[29]
- Trypanosoma cruziexpress cell-surface mucins (PF01456).[30]
Cosmetic use
editUse of skincare products containing snail secretions of mucin have resulted in pain, swelling, and oozing.[31][32]Counterfeit versions of a Korean snail mucin product called COSRX have been selling online, putting users at risk.[33]
See also
editReferences
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- ^Marin F, Corstjens P, de Gaulejac B, de Vrind-De Jong E, Westbroek P (July 2000)."Mucins and molluscan calcification. Molecular characterization of mucoperlin, a novel mucin-like protein from the nacreous shell layer of the fan mussel Pinna nobilis (Bivalvia, pteriomorphia)".The Journal of Biological Chemistry.275(27): 20667–20675.doi:10.1074/jbc.M003006200.hdl:1887/50061.PMID10770949.
- ^Boskey AL (2003). "Biomineralization: an overview".Connective Tissue Research.44 Suppl 1 (1): 5–9.doi:10.1080/713713622.PMID12952166.
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- ^abMoniaux N, Escande F, Porchet N, Aubert JP, Batra SK (October 2001)."Structural organization and classification of the human mucin genes".Frontiers in Bioscience.6:D1192–D1206.doi:10.2741/moniaux.PMID11578969.
- ^Perez-Vilar J, Hill RL (2004). Lennarz WJ, Lane MD (eds.). "Mucin Family of Glycoproteins".Encyclopedia of Biological Chemistry.2.Oxford: Academic Press/Elsevier: 758–764.doi:10.1016/B0-12-443710-9/00411-7.ISBN9780124437104.
- ^Hoorens PR, Rinaldi M, Li RW, Goddeeris B, Claerebout E, Vercruysse J, Geldhof P (March 2011)."Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile".BMC Genomics.12:140.doi:10.1186/1471-2164-12-140.PMC3056801.PMID21385362.
- ^abcKasprzak A, Adamek A (March 2019)."Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis".International Journal of Molecular Sciences.20(6): 1288.doi:10.3390/ijms20061288.PMC6471604.PMID30875782.
- ^Corfield, Anthony P. (2015-01-01)."Mucins: A biologically relevant glycan barrier in mucosal protection".Biochimica et Biophysica Acta (BBA) - General Subjects.1850(1): 236–252.doi:10.1016/j.bbagen.2014.05.003.ISSN0304-4165.PMID24821013.
- ^abMartinez-Carrasco, Rafael; Argüeso, Pablo; Fini, M. Elizabeth (2021-07-01)."Membrane-associated mucins of the human ocular surface in health and disease".The Ocular Surface.21:313–330.doi:10.1016/j.jtos.2021.03.003.ISSN1542-0124.PMC8328898.PMID33775913.
- ^Norman PJ, Norberg SJ, Guethlein LA, Nemat-Gorgani N, Royce T, Wroblewski EE, et al. (May 2017)."Sequences of 95 humanMHChaplotypes reveal extreme coding variation in genes other than highly polymorphicHLA class IandII".Genome Research.27(5): 813–823.doi:10.1101/gr.213538.116.PMC5411776.PMID28360230.
- ^abLang T, Hansson GC, Samuelsson T (October 2007)."Gel-forming mucins appeared early in metazoan evolution".Proceedings of the National Academy of Sciences of the United States of America.104(41): 16209–16214.Bibcode:2007PNAS..10416209L.doi:10.1073/pnas.0705984104.PMC2042186.PMID17911254.
- ^Lang T, Klasson S, Larsson E, Johansson ME, Hansson GC, Samuelsson T (August 2016)."Searching the Evolutionary Origin of Epithelial Mucus Protein Components-Mucins and FCGBP".Molecular Biology and Evolution.33(8): 1921–1936.doi:10.1093/molbev/msw066.PMC4948705.PMID27189557.
- ^Liberelle M, Jonckheere N, Melnyk P, Van Seuningen I, Lebègue N (May 2020). "EGF-Containing Membrane-Bound Mucins: A Hidden ErbB2 Targeting Pathway?".Journal of Medicinal Chemistry.63(10): 5074–5088.doi:10.1021/acs.jmedchem.9b02001.PMID32027502.S2CID211044898.
- ^Xu D, Pavlidis P, Thamadilok S, Redwood E, Fox S, Blekhman R, et al. (August 2016)."Recent evolution of the salivary mucin MUC7".Scientific Reports.6(1): 31791.Bibcode:2016NatSR...631791X.doi:10.1038/srep31791.PMC4997351.PMID27558399.
- ^abFrenkel ES, Ribbeck K (January 2015)."Salivary mucins protect surfaces from colonization by cariogenic bacteria".Applied and Environmental Microbiology.81(1): 332–338.Bibcode:2015ApEnM..81..332F.doi:10.1128/aem.02573-14.PMC4272720.PMID25344244.
- ^Kavanaugh NL, Zhang AQ, Nobile CJ, Johnson AD, Ribbeck K (November 2014). Berman J (ed.)."Mucins suppress virulence traits of Candida albicans".mBio.5(6): e01911.doi:10.1128/mBio.01911-14.PMC4235211.PMID25389175.
- ^abFrenkel ES, Ribbeck K (January 2015)."Salivary mucins in host defense and disease prevention".Journal of Oral Microbiology.7(1): 29759.doi:10.3402/jom.v7.29759.PMC4689954.PMID26701274.
- ^Li Y, Martin LD, Spizz G, Adler KB (November 2001)."MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro".The Journal of Biological Chemistry.276(44): 40982–40990.doi:10.1074/jbc.M105614200.PMID11533058.
- ^Rogers DF (September 2007). "Physiology of airway mucus secretion and pathophysiology of hypersecretion".Respiratory Care.52(9): 1134–46, discussion 1146–9.PMID17716382.
- ^Perez-Vilar J (February 2007)."Mucin granule intraluminal organization".American Journal of Respiratory Cell and Molecular Biology.36(2): 183–190.doi:10.1165/rcmb.2006-0291TR.PMC2176109.PMID16960124.
- ^Morrison CB, Markovetz MR, Ehre C (November 2019)."Mucus, mucins, and cystic fibrosis".Pediatric Pulmonology.54(Suppl 3): S84–S96.doi:10.1002/ppul.24530.PMC6853602.PMID31715083.
- ^Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK (January 2004)."Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis".Cancer Research.64(2): 622–630.doi:10.1158/0008-5472.CAN-03-2636.PMID14744777.
- ^Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N, et al. (March 2006). "Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas".The Prostate.66(4): 421–429.doi:10.1002/pros.20372.PMID16302265.S2CID21904013.
- ^Singh AP, Chaturvedi P, Batra SK (January 2007)."Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy".Cancer Research.67(2): 433–436.doi:10.1158/0008-5472.CAN-06-3114.PMID17234748.
- ^Hanberg, Allen "Medical Surgical Nursing: clinical management for positive outcomes" Black and Hawk (Eds.). ElSevier 2009.
- ^Syed ZA, Härd T, Uv A, van Dijk-Härd IF (August 2008)."A potential role for Drosophila mucins in development and physiology".PLOS ONE.3(8): e3041.Bibcode:2008PLoSO...3.3041S.doi:10.1371/journal.pone.0003041.PMC2515642.PMID18725942.
- ^Cámara ML, Balouz V, Centeno Cameán C, Cori CR, Kashiwagi GA, Gil SA, et al. (May 2019)."Trypanosoma cruzi surface mucins are involved in the attachment to the Triatoma infestans rectal ampoule".PLOS Neglected Tropical Diseases.13(5): e0007418.doi:10.1371/journal.pntd.0007418.PMC6544316.PMID31107901.
- ^McCoy, K.; Class, M. M.; Ricles, V.; Wagoner, G.; Cross, D.; Trautz, A.; Krakowski, A. C. (2024)."Kids These Days: Social Media's Influence on Adolescent Behaviors".The Journal of Clinical and Aesthetic Dermatology.17(5): 40–42.PMC11107899.PMID38779370.
- ^Singh, Nupur; Brown, Angela N.; Gold, Michael H. (2024)."Snail extract for skin: A review of uses, projections, and limitations".Journal of Cosmetic Dermatology.23(4): 1113–1121.doi:10.1111/jocd.16269.PMID38429932.
- ^Amanda Mull (June 17, 2024)."Online Shopping Has Become a Giant Fake Product Machine".Businessweek.RetrievedJune 28,2024.
Further reading
edit- Ali MS, Hutton DA, Wilson JA, Pearson JP (September 2005). "Major secretory mucin expression in chronic sinusitis".Otolaryngology–Head and Neck Surgery.133(3): 423–428.doi:10.1016/j.otohns.2005.06.005.PMID16143194.S2CID42482788.
- Ramsey KA, Rushton ZL, Ehre C (June 2016)."Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins".Journal of Visualized Experiments.112(112): 54153.doi:10.3791/54153.PMC4927784.PMID27341489.
External links
edit- Mucinsat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- "Mucin"atDorland's Medical Dictionary