{"doi":"10.1101/2025.11.13.688363","title":"Rho signaling promotes cell excitability and synaptic transmission","abstract":"Gα  q 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 Gα  q signaling and negatively by Gα  o 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 Ca  2+ activity and stimulated egg laying. Conversely, reducing Rho signaling in the HSNs via expression of Rho-1(T19N) or C3 transferase expression inhibited HSN Ca  2+ activity and egg laying. Animals lacking Rho function in HSN still had vulval muscle Ca  2+ activity that supported contraction and egg release, although this Ca  2+ 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.  <h4>Article Summary</h4>  Rho-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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":6222,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-11-14","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":58284,"name":"Pravat Dhakal","orcid":"0000-0003-4439-0146","position":1,"is_corresponding":false},{"id":58285,"name":"Rossana Signorelli","orcid":null,"position":2,"is_corresponding":false},{"id":58286,"name":"Caroline Case","orcid":null,"position":3,"is_corresponding":false},{"id":58287,"name":"Sana I. Chaudhry","orcid":null,"position":4,"is_corresponding":false},{"id":58288,"name":"Kevin M. Collins","orcid":"0000-0001-9930-0924","position":5,"is_corresponding":false},{"id":58289,"name":"C. Case","orcid":null,"position":6,"is_corresponding":false},{"id":58290,"name":"Sana Chaudhry","orcid":"0000-0003-1559-0974","position":7,"is_corresponding":false},{"id":58283,"name":"Ariana José","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}