PHYSIOLOGY OF MUCIN

SUBMITTED TO: MRS. VANDANA CHAUDHARY

SUBMITTED BY: NITIN

CONTENTS
INTRODUCTION GENES OF MUCIN PROTEIN STRUCTURE GLYCOSYLATION AND AGGREGATION SECRETION CLINICAL SIGNIFICANCE CONCLUSION REFERENCES

INTRODUCTION
High molecular conjugates) weight, heavily glycosylated proteins (glyco-

Produced by epithelial tissues in most metazoans Ability to form gels; therefore secretions, serving functions from lubrication to cell signalling to forming chemical barriers, inhibitory role

Overexpression of the mucin proteins, associated with many types of cancer.

especially

MUC1

is

GENES OF MUCIN

At least 19 human mucin genes have been distinguished by cDNA cloning MUC1, MUC2, MUC3A, MUC3B, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC8, MUC12, MUC13, MUC15, MUC16, MUC17, MUC19, and MUC20.

The major secreted airway mucins are MUC5AC and MUC5B, while MUC2 is secreted mostly in the intestine but also in the airway.

PROTEIN STRUCTURE
composed of two distinct regions The amino- and carboxy-terminal (lightly glycosylated, but rich in cysteines which participate in establishing disulfide bonds). A large central region of multiple repeats of 10 to 80 residue sequences in which up to half are serine or threonine.

Glycosylation And Aggregation

Mucin genes encode mucin monomers that are synthesized as rod-shape apomucin cores that are post-translationally modified by exceptionally abundant glycosylation.

The dense "sugar coating" of mucins gives them considerable waterholding capacity and also makes them resistant to proteolysis, which may be important in maintaining mucosal barriers.
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 million Da. Within these aggregates, monomers are linked to one another mostly by noncovalent interactions, although intermolecular disulfide bonds may also play a role in this process.

SECRETION
Upon stimulation MARCKS (myristylated alanine-rich C kinase substrate) coordinates secretion from mucin filled vesicles.
Fusion of the vesicles to the plasma membrane causes release of the mucin, which as it exchanges Ca2+ for Na+ expands up to 600 fold.

The result is a viscoelastic product of interwoven molecules which, combined with other secretions is called Mucin.

CLINICAL SIGNIFICANCE
Increased mucin production occurs in many adenocarcinomas, including cancers of the pancreas, lung, breast, ovary, colon and other tissues.
overexpressed in lung diseases such as asthma, bronchitis, COPD or cystic fibrosis.

MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process. Mucins are under investigation as possible diagnostic markers for malignancies and other disease processes in which they are most commonly over- or misexpressed. Abnormal deposits of mucin are responsible for the non-pitting facial edema seen in untreated hypothyroidism.

CONCLUSION
The picture that emerges is that of a macromolecule with a complex organization into domains with different structures. From the polymeric view point mucin can be considered as a multi block copolymer with alternating poly electrolytic domains having a grafted sugar brush, connected by flexible regions with less glycosylation and the tendency to form polymers. The molecule has both hydrophobic and hydrophilic regions with the ability to form H-bonds, and electrostatic interactions. This wide range of interactions causes it to aggregate gel and form mucoadhesive interactions with other substances. These physical properties are of direct relevance to the physiological functions of mucus in normal and diseased states. An understanding these properties is of considerable current interest because of the many biomedical applications.

REFERENCES
Bansil R, Stanley E, LaMont JT: Mucin biophysics. Ann Rev Physiol 57:635, 1995.
Gendler SJ, Spicer AP: Physiology 57:607, 1995. Epithelial mucin genes. Ann Rev

Tabak LA: In defense of the oral cavity: Structure, biosynthesis and function of salivary mucins. Ann Rev Physiology 57:547, 1995.

http://en.wikipedia.org/wiki/Mucin