e TCR signal as discussed below and directly through the interactions of ADAP through Ena-VASP family members, which are involved directly in actin polymerization and contribute to regulation of Arp2/3 (Krause et al., 2000). SKAP-55 forms a complex with RIAM (Menasche et al., 2007), which binds to active Rap-1, a small G-protein related to Ras that is required for regulation of adhesion in lymphocytes. Activation of Rap-1 downstream of tyrosine kinase cascades requires a guanine nucleotide exchange factor (GEF) called C3G. TCR signaling activates C3G by a cascade involving Vav, a GEF for Rac (Krawczyk et al., 2002). Recent evidence suggests that Rac activates the WAVE2 complex, which activates Abl and CrkL-C3G to increase active Rap1 (Nolz et al., 2008). The Rap-1-RIAM complex then contributes to activation of talin, which directly binds to the β2 cytoplasmic domain in the critical hinge region to activate and cluster LFA-1 (Smith et al., 2005; Tadokoro et al., 2003; Wegener et al., 2007). This pathway accounts for the strong correlation of LFA-1 dependent cell-cell adhesion and talin accumulation at the interface.
Another connection to F-actin is observed in the APC. DC mediated antigen presentation is an active process that requires small G-proteins of the Rac family and intact F-actin (Al-Alwan et al., 2003; Benvenuti et al., 2004). This may be in part due to the interaction if ICAM-1 with the actin cytoskeleton, in part via ERM family members.
Norcross and Paul first discussed the idea of an immunological synapse with the main “synapse-like” features being a role for Ca2+ elevation, adhesion and directed secretion and polarity (Norcross, 1984). There are a handful of studies in the 1980’s and 90’s that provide quantitative data on cytoskeletal organization, secretory apparatus polarization and Ca2+ signaling in T cell conjugates with B cells e.g. (Geiger et al., 1982; Kupfer et al., 1986; Poenie et al., 1987), in addition to above mentioned studies on adhesion. The classical picture is of cell pairs with a T 