Physiological Regulation of the Immunological Synapse by Agrin

• Published in: Science (American Association for the Advancement of Science) Vol. 292; no. 5522; pp. 1681 - 1686
• Main Authors: Khan, Adil A., Bose, Christian, Yam, Lung S., Soloski, Mark J., Rupp, Fabio
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 01.06.2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Aggregation; Agrin; Agrin - genetics; Agrin - metabolism; Agrin - physiology; Alternative Splicing; Anatomy; Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - physiology; B-Lymphocytes - metabolism; Biological and medical sciences; Cell physiology; Fundamental and applied biological sciences. Psychology; Glycosylation; Immune system; Immunology; Individualized Instruction; Lipids; Lymphocyte Activation; Lymphocytes; Male; Membrane Microdomains - physiology; Membranes; Mice; microdomains; Molecular and cellular biology; Molecules; Muscle fibers; Nerve proteins; Nerve tissue proteins; Neuromuscular Junction - physiology; Neurons; Neurons - physiology; Ova; Physiological aspects; Rafts; Rats; Rats, Sprague-Dawley; Receptor Aggregation; receptor clustering; Receptors; Receptors, Antigen, T-Cell - physiology; Receptors, Cholinergic - physiology; Research Article; Signal Transduction; Splenocytes; T lymphocytes; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Triangulum Galaxy; Aggregation; Signal transduction; Vertebrata; Mammalia; Rat; Agrin; Rodentia; T-Lymphocyte; Activation; Cell surface; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1056594

T cell activation is dependent on both a primary signal delivered through the T cell receptor and a secondary costimulatory signal mediated by coreceptors. Although controversial, costimulation is thought to act through the specific redistribution and clustering of membrane and intracellular kinase-rich lipid raft microdomains at the contact site between T cells and antigen-presenting cells. This site has been termed the immunological synapse. Endogenous mediators of raft clustering in lymphocytes have not been identified, although they are essential for T cell activation. We now demonstrate that agrin, an aggregating protein crucial for formation of the neuromuscular junction, is also expressed in lymphocytes and is important in reorganization of membrane lipid microdomains and setting the threshold for T cell signaling. Our data show that agrin induces the aggregation of signaling proteins and the creation of signaling domains in both immune and nervous systems through a common lipid raft pathway.