was reported as having a high concentration of both CD4 and CD45, but TIRFM imaging of these structures on bilayers does not consistently show this. It is likely that the impression of increased CD4 or CD45 in wide-field imaging is based on the lamellipodium having two plasma membrane layers separated by only 100–200 nm of cytoplasmic and thus appearing twice as bright as surrounding single membrane layers in the pSMAC. In fact, by TIRFM CD45 appears relatively uniform in the synapse except for discrete areas of exclusion around TCR microclusters (Varma et al., 2006). Thus, dSMAC is immunological shorthand for a radial lamellipodium.
The pSMAC must also maintain radial symmetry to have a stable synapse because this structure contains most of the integrins that generate traction for movement (Sims et al., 2007). If the symmetry of the pSMAC is broken the cell will migrate, even if a radially symmetrical dSMAC appears to be maintained. The precise mechanism by which symmetry is established or broken is poorly understood. We know that on the supported planar bilayer system WASP is required to maintain a stable synapse and PKC-θ contributes to symmetry breaking (Sims et al., 2007). Symmetry breaking in the contact plane leads to polarity and in a migrating cells this process is based two opposing actin-myosin networks-the lamellipodium dominated by Rac and a high F-actin:myosin II ratio and the uropod dominated by Rho and a low F-actin:myosin II ratio (Xu et al., 2003). Thus, we have speculated that myosin II may be a target in symmetry breaking. PKC-θ phosphorylates WASP interacting protein (WIP) and regulates its interaction with myosin II (Krzewski et al., 2006). WASP also interacts with this complex. One hypothesis is that myosin II activation via WIP phosphorylation leads to contraction of the pSMAC actin network leading to local thinning and breakdown, whereas WASP may either antagonize this myosin II activation or induced ventral actin polymerization to repair the pSMAC and restore symmetry after its been brok