Physiological regulation of the immunological synapse by agrin

T cell activation is dependent on both a primary signal delivered through t he T cell receptor and a secondary costimulatory signal mediated by corecep tors. Although controversial, costimulation is thought to act through the s pecific redistribution and clustering of membrane and intracellular kinase- rich Lipid raft microdomains at the contact site between T cells and antige n-presenting cells. This site has been termed the immunological synapse. En dogenous mediators of raft clustering in lymphocytes have not been identifi ed, although they are essential for T cell activation. We now demonstrate t hat agrin, an aggregating protein crucial for formation of the neuromuscula r junction, is also expressed in Lymphocytes and is important in reorganiza tion of membrane Lipid microdomains and setting the threshold for T cell si gnaling. Our data show that agrin induces the aggregation of signaling prot eins and the creation of signaling domains in both immune and nervous syste ms through a common Lipid raft pathway.