Cloning of the mucosal addressin MAdCAM-1 from human brain: identification of novel alternatively spliced transcripts.
The mucosal addressin cell adhesion molecule-1 (MAdCAM-1), expressed selectively on high endothelial venules (HEV) and lamina propria venules, directs lymphocyte traffic by binding the lymphocyte Peyer's patch adhesion molecule-1 (LPAM-1, alpha 4 beta 7). Full-length DNA encoding human MAdCAM-1 was obtained by combining sequences from an expressed sequence tag (EST) identified in an early stage human brain cDNA library, a polymerase chain reaction-derived clone, and a MAdCAM-1 genomic clone. The deduced amino acid sequence revealed an 18 amino acid signal peptide, two N-terminal immunoglobulin (Ig)-like domains conserved (59-65%) in sequence with those of the mouse homologue, an 86 amino acid mucin-like region rich in serine-threonine residues, a 20 amino acid transmembrane domain and a 43 amino acid charged cytoplasmic domain. No counterpart to the third IgA-like domain of mouse MAdCAM-1 was present; however, the serine-threonine-rich mucin domain was extended as two distinguishable major and minor mucin regions unrelated to the mouse domain. The major domain is formed from six tandem repeats of an eight amino acid sequence having the MUC-2-related consensus DTTSPEP/SP. Human MAdCAM-1 mRNA transcripts were restricted to small intestine, colon, spleen, pancreas and brain. Alternatively spliced MAdCAM-1 variants were identified that lack parts of the second Ig domain and all or part of the major mucin domain, indicating that the function of this vascular addressin is regulated by extensive modifications to its multi-domain structure.
Leung
E
E
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Greene
J
J
Ni
J
J
Raymond
L G
LG
Lehnert
K
K
Langley
R
R
Krissansen
G W
GW
D017398:Alternative Splicing / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D001923:Brain Chemistry / Q000235:genetics*; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics* / Q000302:isolation & purification*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000032:analysis / Q000235:genetics* / Q000302:isolation & purification*; D009092:Mucous Membrane / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000276:immunology*
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing