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Science 292 (5522): 1681-1686

Copyright © 2001 by the American Association for the Advancement of Science

Physiological Regulation of the Immunological Synapse by Agrin

Adil A. Khan,12* Christian Bose,2 Lung S. Yam,2 Mark J. Soloski,3 Fabio Rupp2dagger

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.

1 Outer Banks Neuroscience, Baltimore, MD 21218, USA.
2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed: outerbanksneuro{at}yahoo.com

dagger    Present address: Hyseq Inc., Sunnyvale, CA 94085, USA.

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