Glia Promote Synaptogenesis Through IQGAP

Synapses are fundamental to the normal functioning of the nervous system. Glia play a pivotal role in regulating synaptic formation. However, how presynaptic neurons assemble synaptic structure in response to the glial signals remains largely unexplored. To address this question, we use cima-1 mutant C. elegans as an in vivo model, in which the VCSC glial processes contact to the ectopic neurite region and thereby promoting the ectopic synapse formation at adult stage. Through RNAi screen, we found that presynaptic Rho GTPase CDC-42 and IQGAP PES-7 are required for VCSC glia-induced synaptic formation. Additionally, we found that cdc-42 and pes-7 are only required but also sufficient for normal synaptogenesis during postembryonic developmental stages. Mechanistically, the glia-neurite contact sites, PES-7 activated by CDC-42 promotes presynaptic formation through regulating F-actin assembly. Our data provide new insights into the molecular mechanisms by which presynaptic neurons assemble synaptic structures in response to synaptogenesis signals from glia during post embryonic development. Our results indicate that CDC-42 and PES-7 play critical roles in the temporal regulation of synaptic spatial specificity. Given the evolutionary conservation of CDC-42 and IQGAPs, we speculate that our findings in C. elegans apply to vertebrates.