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Beschreibung

Mucosal addressin cell adhesion molecule 1 (UniProt: Q61826, also known as MAdCAM-1, mMAdCAM-1) is encoded by the Madcam1 gene (Gene ID: 17123) in murine species. MAdCAM-1 is a cell adhesion leukocyte receptor that helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and the intestinal lamina propria. It is highly expressed on high endothelial venules (HEV) of organized intestinal lymphoid tissues and mesenteric lymph nodes, and in the lamina propria of the intestine. Its expression is also observed in brain endothelioma cells and mucosal tissues during chronic inflammation. Aberrant expression of MAdCAM-1 has also been reported in the inflamed pancreas. MAdCAM-1 can bind both the integrin alpha-4/beta-7 and L-selectin and is involved in regulating both the passage and retention of leukocytes. It is synthesized with a signal peptide (aa 1-21), which is subsequently cleaved off in mature form. MAdCAM-1 has an extracellular domain (aa 22-109), a transmembrane domain (aa 365-385), and a cytoplasmic domain (aa 386-405). It also contains three Ig-like domains (aa 22-109, 110-227, 258-357) and a Mucin-like region (aa 221-257). Two isoforms of MAdCAM-1 have been described that are produced by alternative splicing. Both isoforms can adhere to integrin alpha-4/beta-7. Isoform 2 that lacks the mucin-like domain is believed to be specialized in supporting integrin alpha-4/beta-7-dependent adhesion strengthening, independent of L-selectin binding. Interaction between integrin alpha 4 and MAdCAM-1 is considered to be important for the homing of diabetogenic T cells to the pancreas. (Ref.: Savinov, AY., et al. (2003). J. Exp. Med. 197(5), 643-656, Rivera-Nieves, J., et al. (2005). J. Immunol. 174(4), 2343-2352).