Rho signaling promotes cell excitability and synaptic transmission

Gq signaling through Trio RhoGEF and Phospholipase C effectors promotes neurotransmitter release at synapses. Whether activated Rho and Phospholipase C signaling acts through shared or independent pathways remains unclear. We use the egg-laying circuit of C. elegans, which is regulated positively by Gq signaling and negatively by Go signaling, to determine the role of Rho GTPase in G-protein regulation of neural circuit excitability. We previously showed that Trio signals in both the presynaptic Hermaphrodite-Specific command Neurons (HSNs) and the postsynaptic egg-laying vulval muscles they innervate to promote egg laying. Here we show that its effector Rho similarly signals both pre- and post-synaptically. Expression of constitutively active Rho-1(G14V) in either the HSNs or vulval muscles increased their Ca2+ activity and stimulated egg laying. Conversely, reducing Rho signaling in the HSNs via expression of Rho-1(T19N) or C3 transferase expression inhibited HSN Ca2+ activity and egg laying. Animals lacking Rho function in HSN still had vulval muscle Ca2+ activity that supported contraction and egg release, although this Ca2+ activity lacked the enhancement associated with HSN neurotransmitter release, suggesting it was largely driven by stretch-dependent feedback. Together, these results show that Rho signals in both the HSNs and vulval muscles to promote excitability and egg laying. Article SummaryRho-type G-proteins have been extensively studied for their role in neural development, but accumulating evidence points to a role in regulating synaptic transmission and neural circuit activity. Using powerful in vivo imaging and genetic techniques in the nematode Caenorhabditis elegans, the authors show that Rho signals in both presynaptic neurons and postsynaptic muscles to promote circuit activity and behavior. These findings solidify Rho as a key regulator of neurotransmitter signaling.