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Group leader: This email address is being protected from spambots. You need JavaScript enabled to view it. (Professor, Ph.D.)
Members: Malin Bäckström (scientist, Ph.D.), Hasse Karlsson (scientist, Ph.D.), Emily Malmberg (postdoc, Ph.D.), Tina Thomsson (postdoc, Ph.D.), Ana Rodriguez-Pinero (postdoc, Ph.D.), Ylva Andersch-Björkman (Ph.D. student), Jessica Holmén (Ph.D. student), Malin Johansson (Ph.D. student), Taher Pelaseyed (Ph.D. student), Lang Tiange (Ph.D. student), Åsa Petersson (technician), and Maléne By (technician)

The Mucin Biology Group at MIVAC is studying the structure and function of mucins (mucus glycoproteins). ghThis includes most aspects of mucins including also their glycan parts. A special focus is on the gastrointestinal tract and the role of mucins in the protection of the intestine and as part of the intestinal innate immune system. This also includes mucins in relation to the CFTR channel defect in cystic fibrosis and to colon cancer development.

Mucins are extracellular large highly glycosylated molecules with mucin domains. Mucin domains are rich in the amino acids threonine, serine and proline, where the oligosaccharides are linked via N-acetylgalactosamine to the hydroxy amino acids. Usually these molecules have more than 50% of their mass due to glycans. There are two types of mucins, secreted and membrane bound. Most of the secreted mucins are gel-forming due to their polymeric nature. The major mucin of the gastrointestinal tract is called MUC2 and is produced by the intestinal goblet cells. The apoprotein of this mucin has two central mucin domains and cysteine-rich domains at both the N- and C-termini. The primary translational product is quickly dimerized in its C-terminus in the endoplasmic reticulum and O-glycans added in the Golgi apparatus to reach a mass of about 5 million Da. The MUC2 mucin is sorted to secretory vesicles and forms trimers in its N-termini giving a net-like gel structure. The MUC2 mucin build up the almost millimeter thick mucus layer protecting the colon and act as a physical barrier that can only be penetrated by for example the parasite Entamoeba histolytica that dissolves the mucus by a specific proteolytic cleavage in MUC2.

Mice lacking the Muc2 mucin have no adherent mucus and are very susceptible to experimental ulcerative colitis and infections. When the glycan parts of the MUC2 mucin was analyzed from millimeter-sized human colon biopsies, altered glycosylation was found among the patients with an active colitis. We are actively addressing inflammatory caused alterations in the components of the colon mucus layer as part of the mucosal barrier in ways to further understand the inflammatory bowel disease ulcerative colitis.

The transmembrane mucins are cleaved by an autocatalytic mechanism, but held together as heterodimers at the outside of the membrane. These mucins probably act as sensors and the MUC1 mucin has been shown to take part in the regulation of mucus amounts in cystic fibrosis mice. By alterations in its glycosylation, the MUC1 mucin is a well-known tumor antigen that can elicit an immune response. We have also developed large-scale recombinant production of the MUC1 extracellular part with variable glycosylation for cancer vaccine studies.

Important publications:
Godl K, Johansson MEV, Karlsson H, Mörgelin M, Lidell ME, Olson FJ, Gum Jr JR, Young S, Kim YS and Hansson GC. (2002) The N-termini of the MUC2 mucin form trimers that are held together within a trypsin-resistant core fragment. J. Biol Chem., 277:47248-47256.

Lidell M, Johansson MEV, and Hansson GC. (2003) An autocatalytic cleavage in the Human MUC2 Mucin C-terminus occurs at the low pH of the late secretory pathway. J. Biol. Chem. 278:13944-13951.

Lidell M, Moncada D, Chadee K, and Hansson GC. (2006) Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal part and dissolves the protective colonic mucus gel. Proc Natl Acad Sci USA, 103:9298-9303.

Hansson group