Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders

Figure 1

Regulation and interaction of Rac1-related signaling pathways at the postsynaptic terminal. Effectors of FXS and Huntington’s disease, such as FMRP and HTT, can directly activate or inhibit Rac1 activity to modulate its downstream signaling cascades, mainly via the Rac1-PAK-cofilin pathway, which subsequently influences synaptic plasticity. In schizophrenia, NMDA receptors activate Kal-7 via TIAM1, while DISC1 and NRG1/ErbB4 interact with Kal-7 to activate or inhibit Rac1. In ASD, SHANK3 directly modulates Rac1 activity, while other effectors like AUTS2, P-Rex-1, and Elmo2/Dock180 form a complex to modulate Rac1 activity and then affect NMDA receptor activity through the PAK pathway. In Rett syndrome, BDNF activates TrkB receptors to modulate the activity of CDKL5 and MECP2 that further regulate the function of the Rac1-cofilin pathway. Abnormalities of these proteins in any pathways may affect neuroplasticity and cause neurodevelopmental disorders.