FIGURE 1.

Rac GTPase activity is regulated by synaptic activation through synaptic receptors that are known to be involved in memory formation such as NMDA, Trk, and Eph receptors. Activation of these synaptic receptors leads to the regulation of RacGEFs or RacGAPs that activate or inhibit Rac GTPase, respectively. Rac GTPase regulates downstream effectors that can affect spine morphology and synaptic transmission. Rac GTPase exerts its effects on spine morphology through the regulation of molecules that affect signaling pathways that control actin-regulatory proteins. In its active state, Rac GTPase activates the PAK-LIMK-cofilin pathway that can control actin dynamics through the inhibition of cofilin, an actin-depolymerizing protein. Rac GTPase also regulates actin network through the modulation of the WAVE-Arp2/3 pathway that, in turn, regulates actin nucleation and actin branching. Both cofilin and Arp2/3 regulation of the actin cytoskeleton affect spine morphology. In addition, Rac GTPase may regulate synaptic efficacy by controlling AMPA receptor content in the synapse. Rac1 GTPase protein level in the spine and its effects on spine functions can be regulated by calcium-induced translocation of Rac1 GTPase into the spine by copine-6. The correlation between Rac GTPase activity and changes in spine morphology, synaptic transmission and memory indicates that Rac GTPase regulates spine functions that can mediate various stages of memory formation, erasure, extinction and forgetting.