Interplay of Polarity Proteins and GTPases in T-Lymphocyte Function
Figure 1
GTPases are important mechanical switches in T-lymphocyte function. (a) During antigen presentation, a T-cell undergoes dramatic changes in protein localization and morphology. The polarity protein, Scribble, is believed to be recruited to the synapse after TCR signaling and, through its potential association with βPIX, may recruit Rac1 and Cdc42 to close proximity to GEFs such as Vav. Activated Rac1 and Cdc42 in turn, activate downstream effectors such as WAVE, WASP, and PAK, enabling actin polymerization and thus, changes in morphology. (b) In a migrating T-cell, GTPases regulate actin polymerization to allow for cell moment. At the leading edge of the cell, Cdc42 is activated by the Ras-related protein RAP1a, which in turns activates members of the Par complex. Par3 recruits a RAC GEF, Tiam1, which in turn activates Rac1. Rac1 promotes actin reorganization, thus lamellipodium formation through proteins such as WAVE and Arp2/3. The Par complex also binds and activates the E3 ligase Smurf1. Smurf1 promotes degradation of another GTPase, RhoA, which, in its active form enables actin contractility in cells.
