Expression of the mouse fragilis gene products in immune cells and association with receptor signaling complexes

• Published in: Genes and immunity Vol. 7; no. 2; pp. 113 - 121
• Main Authors: Smith, R A, Young, J, Weis, J J, Weis, J H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-03-2006
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antigens, CD - genetics; Antigens, CD - physiology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Blotting, Western; Bone marrow; CD19 antigen; CD81 antigen; CD9 antigen; Cell activation; Cell proliferation; Cells; Cellular signal transduction; Chromosomes; Conserved Sequence; Flow Cytometry; Gene expression; Genes; Genetic aspects; Genome; Genomes; Health aspects; Immune response; Immunology; Introns; Kinases; L-selectin; Lipid rafts; Lipids; Lymphocyte Activation - genetics; Lymphocytes B; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Membrane Microdomains - genetics; Membrane Microdomains - immunology; Membrane Microdomains - metabolism; Membrane Proteins - chemistry; Membrane Proteins - immunology; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Monoclonal antibodies; Physiological aspects; Precipitin Tests; Protein Structure, Tertiary; Proteins; Receptor mechanisms; Receptors, Antigen, B-Cell - metabolism; Receptors, Antigen, B-Cell - physiology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Signal Transduction - immunology; Tetraspanin 28; Tetraspanin-29; Transmembrane domains; United States
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364278

The mouse genome possesses five genes encoding proteins homologous to human Leu-13. The Leu-13 protein associates with immune cell receptor activation complexes: a monoclonal antibody against Leu-13 induces T and B cells to form homotypic aggregates, inhibits activation-induced proliferation and induces the shedding of L-selectin. The mouse fragilis proteins have not been previously analyzed as components of the immune response. Antibody and nucleic acid reagents were generated that are specific for each of the five fragilis gene products. Expression of some of these genes (fragilis and fragilis3) is wide spread in a variety of mouse immune (and nonimmune) tissues while others (fragilis5) appear to be much more restricted. These proteins have been predicted to span the membrane twice with both amino- and carboxyl-terminal sequences extracellular: we show that a highly conserved loop of the protein between the transmembrane domains is intracellular. The fragilis proteins are associated with tetraspanin proteins CD81 and CD9: B cell activation positions fragilis into lipid rafts along with the CD81, CD19, and CD21. The mouse functional equivalent to human Leu-13 may not be single gene product, but instead may require the contribution of multiple fragilis proteins.