Hypothesis for agrin regulation of immunological synapse formation. (a) Raft-aggregating activity of agrin proteoglycan is regulated by intramolecular interaction with heparan sulfate chains. (b) When these chains are degraded by the lymphocyte heparanase, the raft-aggregating activity is expressed. (c) Recent evidence indicates that T cell agrin glycoprotein (agrinact) enhances synapse formation and T cell activation. Conversely, if agrin glycoprotein is prevented from entering the synapse, perhaps through an interaction with laminin or other ECM components, the formation of the synapse may be destabilized by ectopic raft aggregates, thus preventing T cell activation. Thus, in the presence of specific ECM components, the effect of actin conversion from proteoglycan to glycoprotein may be inhibitory, whereas in an ECM-depleted site like a lymph node it may enhance responses.
