Home LiteratureArticle Details
PMID: 9480884 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sialomucin complex in the rat respiratory tract: a model for its role in epithelial protection.

The Biochemical journal ·Vol. 330 ( Pt 2) ·1998-03-01 ·Pages 737-44

McNeer RR, Huang D, Fregien NL, Carraway KL

Abstract

The pulmonary epithelium has a multitude of specialized functions, which depend on regulated growth and differentiation of several cell types. One such function is the synthesis and secretion of mucins, which offer the epithelium protection from and a means for removal of noxious environmental factors. Sialomucin complex (SMC) is a heterodimeric glycoprotein consisting of a mucin subunit (ASGP-1, ascites sialoglycoprotein-1) and a transmembrane protein (ASGP-2) with two epidermal-growth-factor-like domains. SMC was originally discovered in a highly metastatic rat mammary adenocarcinoma and has been implicated in metastasis and in the protection of the tumour cells from natural killer cells. It can also act as a ligand for the receptor tyrosine kinase 185(neu), suggesting that it is bifunctional as well as heterodimeric. SMC is expressed on the epithelium of rat conducting airways, with the highest levels occurring in the proximal trachea and progressively decreasing into the bronchioles. Airway SMC consists of two forms: a soluble form that lacks the C-terminal cytoplasmic and transmembrane domains and accounts for about 70% of the total, and a membrane-associated form that has the C-terminal domains. Immunocytochemical analyses show that SMC is predominantly present on the apical surfaces of the airway epithelium, but not in goblet cells. Soluble form can be removed from the trachea by rinsing, suggesting that a fraction of the protein is adsorbed to the apical surface. Based on these results, we propose a protective mechanism in which membrane and soluble forms of SMC are produced by airway luminal epithelial cells to provide a cell-associated epithelial glycoprotein barrier that also serves as an interface with flowing mucus. In support of this mechanism, we demonstrated secretion of soluble SMC by primary cultures of tracheal epithelial cells. This model suggests that SMC is a critical element in the protective barrier of the airway epithelium.

MeSH Terms
Animals Cells, Cultured Epithelial Cells/chemistry,physiology Female Models, Biological Mucin-4 Mucins/physiology Rats Rats, Inbred F344 Respiratory Physiological Phenomena Respiratory System/chemistry,cytology Sialoglycoproteins/physiology Sialomucins
Chemicals
Mucin-4 Mucins Sialoglycoproteins Sialomucins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McNeer R R
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, FL 33101, USA.
Huang D
Fregien N L
Carraway K L
References (46)
46 references, click to expand
  1. Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu.
    Oncogene. 1994 Nov;9(11):3139-47 PMID: 7936636
  2. Human respiratory mucins.
    Eur Respir J. 1992 Feb;5(2):247-56 PMID: 1559590
  3. Epithelial mucin genes.
    Annu Rev Physiol. 1995;57:607-34 PMID: 7778880
  4. Cystic fibrosis: molecular biology and therapeutic implications.
    Science. 1992 May 8;256(5058):774-9 PMID: 1375392
  5. Antibodies to the cytoplasmic domain of the MUC1 mucin show conservation throughout mammals.
    Biochem Biophys Res Commun. 1992 May 29;185(1):167-75 PMID: 1599454
  6. Molecular cloning of the transmembrane component of the 13762 mammary adenocarcinoma sialomucin complex. A new member of the epidermal growth factor superfamily.
    J Biol Chem. 1992 Aug 15;267(23):16341-6 PMID: 1379596
  7. Cell surface mucin-type glycoproteins and mucin-like domains.
    Glycobiology. 1991 Mar;1(2):131-8 PMID: 1823156
  8. Cell membrane-associated mucins and their adhesion-modulating property.
    Trends Biochem Sci. 1992 Sep;17(9):359-63 PMID: 1412714
  9. Mucins: structure, function, and role in pulmonary diseases.
    Am J Physiol. 1992 Oct;263(4 Pt 1):L413-29 PMID: 1415719
  10. Tumor sialomucin complexes as tumor antigens and modulators of cellular interactions and proliferation.
    J Cell Sci. 1992 Oct;103 ( Pt 2):299-307 PMID: 1478934
  11. Association of p185neu with microfilaments via a large glycoprotein complex in mammary carcinoma microvilli. Evidence for a microfilament-associated signal transduction particle.
    J Biol Chem. 1993 Mar 15;268(8):5582-7 PMID: 8095497
  12. Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization.
    J Histochem Cytochem. 1993 Oct;41(10):1479-85 PMID: 8245407
  13. Molecular cloning and sequencing of the mucin subunit of a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat mammary adenocarcinoma cells.
    J Biol Chem. 1994 Apr 22;269(16):11950-5 PMID: 8163496
  14. Identification of two major populations of mucins in respiratory secretions.
    Am J Respir Crit Care Med. 1994 Sep;150(3):823-32 PMID: 8087358
  15. Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway.
    J Virol. 1995 Oct;69(10):5951-8 PMID: 7545239
  16. The epithelial mucin, MUC1, of milk, mammary gland and other tissues.
    Biochim Biophys Acta. 1995 Dec 20;1241(3):407-23 PMID: 8547303
  17. Respiratory mucins: identification of core proteins and glycoforms.
    Biochem J. 1996 Jun 15;316 ( Pt 3):967-75 PMID: 8670177
  18. A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.
    Mol Biol Cell. 1996 Apr;7(4):565-77 PMID: 8730100
  19. Efficient adenovirus-mediated gene transfer to basal but not columnar cells of cartilaginous airway epithelia.
    Hum Gene Ther. 1996 May 20;7(8):921-31 PMID: 8727506
  20. Mucociliary clearance in the airways.
    Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1868-902 PMID: 8970383
  21. Sialomucin complex, a heterodimeric glycoprotein complex. Expression as a soluble, secretable form in lactating mammary gland and colon.
    J Biol Chem. 1996 Dec 27;271(52):33476-85 PMID: 8969211
  22. Identification of two glycoforms of the MUC5B mucin in human respiratory mucus. Evidence for a cysteine-rich sequence repeated within the molecule.
    J Biol Chem. 1997 Apr 4;272(14):9561-6 PMID: 9083100
  23. Roles of ErbB-3 and ErbB-4 in the physiology and pathology of the mammary gland.
    J Mammary Gland Biol Neoplasia. 1997 Apr;2(2):187-98 PMID: 10882304
  24. Purification and properties of the major sialoglycoprotein of the milk fat globule membrane.
    Arch Biochem Biophys. 1977 Mar;179(2):690-6 PMID: 851364
  25. Purification of the major sialoglycoproteins of 13762 MAT-B1 and MAT-C1 rat ascites mammary adenocarcinoma cells by density gradient centrifugation in cesium chloride and guanidine hydrochloride.
    J Biol Chem. 1980 Jan 25;255(2):783-90 PMID: 7356644
  26. A complex of two cell surface glycoproteins from ascites mammary adenocarcinoma cells.
    J Biol Chem. 1980 Dec 25;255(24):12051-9 PMID: 7440586
  27. Cell-surface macromolecular and morphological changes related to allotransplantability in the TA3 tumor.
    Biomembranes. 1983;11:207-58 PMID: 6338947
  28. Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule.
    Somatic Cell Genet. 1983 Jul;9(4):415-27 PMID: 6353626
  29. Structures of the O-linked oligosaccharides of the major cell surface sialoglycoprotein of MAT-B1 and MAT-C1 ascites sublines of the 13762 rat mammary adenocarcinoma.
    J Biol Chem. 1984 Apr 25;259(8):4866-77 PMID: 6715325
  30. Comparative studies of mucus and mucin physicochemistry.
    Ciba Found Symp. 1984;109:196-211 PMID: 6569837
  31. Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.
    Exp Lung Res. 1985;9(3-4):289-308 PMID: 4076055
  32. Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium.
    Proc Natl Acad Sci U S A. 1987 Sep;84(17):6060-4 PMID: 2888110
  33. Stage- and tissue-specific expression of the neu oncogene in rat development.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8498-501 PMID: 3317411
  34. Human neutrophil elastase releases cell surface mucins from primary cultures of hamster tracheal epithelial cells.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):9304-8 PMID: 3480544
  35. Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2320-3 PMID: 2895474
  36. Isolation and partial characterization of ascites sialoglycoprotein-2 of the cell surface sialomucin complex of 13762 rat mammary adenocarcinoma cells.
    Biochem J. 1990 Jan 1;265(1):121-9 PMID: 2302161
  37. Mechanisms of airway goblet cell mucin release: studies with cultured tracheal surface epithelial cells.
    Am J Respir Cell Mol Biol. 1989 Aug;1(2):137-43 PMID: 2695148
  38. Biosynthesis of the cell surface sialomucin complex of ascites 13762 rat mammary adenocarcinoma cells from a high molecular weight precursor.
    J Biol Chem. 1990 May 25;265(15):8505-10 PMID: 2111320
  39. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues.
    Oncogene. 1990 Jul;5(7):953-62 PMID: 1973830
  40. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin.
    J Biol Chem. 1990 Sep 5;265(25):15286-93 PMID: 1697589
  41. Why are proteins O-glycosylated?
    Trends Biochem Sci. 1990 Aug;15(8):291-4 PMID: 2204153
  42. Mucin in disease. Modification of mucin gene expression in airway disease.
    Am Rev Respir Dis. 1991 Sep;144(3 Pt 2):S38-41 PMID: 1892324
  43. Mucin structure. The structure and heterogeneity of respiratory mucus glycoproteins.
    Am Rev Respir Dis. 1991 Sep;144(3 Pt 2):S4-9 PMID: 1892325
  44. Cell-associated episialin is a complex containing two proteins derived from a common precursor.
    J Biol Chem. 1992 Mar 25;267(9):6171-7 PMID: 1556125
  45. Suppression of cellular aggregation by high levels of episialin.
    Cancer Res. 1992 Apr 15;52(8):2318-24 PMID: 1559234
  46. Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.
    J Cell Biol. 1995 Apr;129(1):255-65 PMID: 7698991
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Published
1998-03-01
Pages
737-44
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1219199
Subset
IM
Grants
NCI NIH HHS · CA 14395 · United States
NCI NIH HHS · CA 52498 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com