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 lymphocyte trafficking. MAdCAM-1 is a multifunctional type l transmembrane adhesion molecule comprising two distal lg domains involved in alpha 4 beta 7 integrin binding, a mucin-like region able to display L-selectin-binding carbohydrates, and a membrane-proximal lg domain homologous to lgA. We show in this work that the MAdCAM-1 gene is located on chromosome 10 and contains five exons. The signal peptide and each one of the three lg domains are encoded by a distinct exon, whereas the transmembrane, cytoplasmic tail, and 3'-untranslated region of MAdCAM-1 are combined on a single exon. The mucin-like region and the third lg domain are encoded together on exon 4. An alternatively spliced MAdCAM-1 mRNA is identified that lacks the mucin/lgA-homologous exon 4-encoded sequences. This short variant of MAdCAM-1 may be specialized to support alpha 4 beta 7-dependent adhesion strengthening, independent of carbohydrate-presenting function. Sequences 5' of the transcription start site include tandem nuclear factor-kappa B sites; AP-1, AP-2, and signal peptide-1 binding sites; and an estrogen response element. Our findings reinforce the correspondence between the multidomain structure and versatile functions of this vascular addressin, and suggest an additional level of regulation of carbohydrate-presenting capability, and thus of its importance in lectin-mediated vs alpha 4 beta 7-dependent adhesive events in lymphocyte trafficking.
Sampaio
S O
SO
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Li
X
X
Takeuchi
M
M
Mei
C
C
Francke
U
U
Butcher
E C
EC
Briskin
M J
MJ
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005796:Genes; D007136:Immunoglobulins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000235:genetics*; D017421:Sequence Analysis; D014158:Transcription, Genetic / Q000235:genetics*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins