ORGANIZATION, REGULATORY SEQUENCES, AND ALTERNATIVELY SPLICED TRANSCRIPTS OF THE MUCOSAL ADDRESSIN CELL-ADHESION MOLECULE-1 (MADCAM-1) GENE

The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is expressed selectively at venular sites of lymphocyte extravasation into mucosal lymphoid tissues and lamina propria, where it directs local lymphocyt e trafficking. MAdCAM-1 is a multifunctional type I transmembrane adhe sion molecule comprising two distal Ig domains involved in alpha 4 bet a 7 integrin binding, a mucin-like region able to display L-selectin-b inding carbohydrates, and a membrane-proximal Ig domain homologous to IgA. We show in this work that the MAdCAM-1 gene is located on chromos ome 10 and contains five exons. The signal peptide and each one of the three Ig domains are encoded by a distinct exon, whereas the transmem brane, cytoplasmic tail, and 3'-untranslated region of MAdCAM-1 are co mbined on a single exon. The mucin-like region and the third Ig domain are encoded together on exon 4. An alternatively spliced MAdCAM-1 mRN A is identified that lacks the mucin/IgA-homologous exon 4-encoded seq uences. This short variant of MAdCAM-1 may be specialized to support a lpha 4 beta 7-dependent adhesion strengthening, independent of carbohy drate-presenting function. Sequences 5' of the transcription start sit e include tandem nuclear factor-kappa B sites; AP-1, AP-2, and signal peptide-1 binding sites; and an estrogen response element. Our finding s reinforce the correspondence between the multidomain structure and v ersatile functions of this vascular addressin, and suggest an addition al level of regulation of carbohydrate-presenting capability, and thus of its importance in lectin-mediated vs alpha 4 beta 7-dependent adhe sive events in lymphocyte trafficking.