A. Both phagocytosis and excitatory synaptogenesis require Rac1 activation. The adhesion-GPCR BAI1 regulates both processes by signaling through different Rac1-GEFs. The C-terminus of BAI1 interacts with Tiam1 through a TEV motif and DOCK180 via ELMO through a helical region (HR). Tiam1 and DOCK180 associate with divergent protein complexes capable of generating distinct Rac1 signaling that promotes synaptogenesis or phagocytosis, respectively.
B. At excitatory synapses, Rac1 is activated by EphB2 and NMDA-type glutamate receptors (NMDARs) via the Rac1-GEFs Tiam1 and Kalirin-7. These Rac1-GEFs signal through parallel pathways to promote spino- and synaptogenesis. Loss of either protein elicits a phenotype, proving that they are not redundant.