A PDZ-RapGEF promotes synaptic development in Caenorhabditis elegans through a Rap/Rac signaling pathway

Small G proteins coordinate the development of nerve terminals. The activity of G proteins is finely tuned by GTPase regulatory proteins. Previously, we have observed that PXF-1, a Caenorhabditis elegans GTPase regulatory protein, is required for the function of cholinergic motor neurons. Here, we investigated how PXF-1 coordinates the development of presynaptic terminals at the molecular level. We observed that PXF-1 acts through RAP-1 to promote synapse development. Subsequently, we found that pxf-1 mutants display a reduction in RAC-2 activity, which is required for cholinergic synapse development. We observed that RAC-2 acts downstream of RAP-1. Finally, we identified a physical interaction between RAP-1 and TIAM-1, a Rac guanine exchange factor, which links PXF-1 function to the presynaptic actin cytoskeleton through RAC-2 activation. These findings highlight how small G protein signaling pathways interact to coordinate the development of presynaptic terminals.