Glia Promote Synaptogenesis through an IQGAP PES-7 in C. elegans.

Synapses are fundamental to the normal function 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 astrocyte-like VCSC glial processes ectopically reach an asynaptic neurite region and promote presynaptic formation there. Through an RNAi screen, we find that the Rho GTPase CDC-42 and IQGAP PES-7 are required in presynaptic neurons for VCSC glia-induced presynaptic formation. In addition, we find that cdc-42 and pes-7 are also required for normal synaptogenesis during postembryonic developmental stages. PES-7 activated by CDC-42 promotes presynaptic formation, most likely through regulating F-actin assembly. Given the evolutionary conservation of CDC-42 and IQGAPs, we speculate that our findings in C. elegans apply to vertebrates. • CDC-42 and IQGAP PES-7 are required for glia-mediated synaptogenesis • PES-7 acts downstream of CDC-42 to promote synaptic formation • CHD and GRD domains of PES-7 are required for synaptogenesis • PES-7 promotes synaptogenesis, most likely through F-actin Dong et al. reveal a role of the conserved CDC-42 and IQGAP/PES-7 in glia-mediated synaptogenesis during postembryonic development. At the glia-neurite contact sites, PES-7 activated by CDC-42 promotes presynaptic formation, possibly through regulating the F-actin assembly, providing insight into the neuronal responses to pro-synaptic signaling from glia. [ABSTRACT FROM AUTHOR]