{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:24Z","timestamp":1785411384263,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,14]]},"group-title":"Neuroscience","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["NS086932"],"award-info":[{"award-number":["NS086932"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["20PRE35210233"],"award-info":[{"award-number":["20PRE35210233"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  G\u03b1\n                  <jats:sub>q<\/jats:sub>\n                  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\n                  <jats:italic>C. elegans<\/jats:italic>\n                  , which is regulated positively by G\u03b1\n                  <jats:sub>q<\/jats:sub>\n                  signaling and negatively by G\u03b1\n                  <jats:sub>o<\/jats:sub>\n                  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\n                  <jats:sup>2+<\/jats:sup>\n                  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\n                  <jats:sup>2+<\/jats:sup>\n                  activity and egg laying. Animals lacking Rho function in HSN still had vulval muscle Ca\n                  <jats:sup>2+<\/jats:sup>\n                  activity that supported contraction and egg release, although this Ca\n                  <jats:sup>2+<\/jats:sup>\n                  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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Article Summary<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging and genetic techniques in the nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , 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.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.13.688363","type":"posted-content","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T02:30:18Z","timestamp":1763173818000},"source":"Crossref","is-referenced-by-count":0,"title":["Rho signaling promotes cell excitability and synaptic transmission"],"prefix":"10.64898","author":[{"given":"Ariana","family":"Jos\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravat","family":"Dhakal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Signorelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Case","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana I.","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9930-0924","authenticated-orcid":false,"given":"Kevin M.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025111716300643000_2025.11.13.688363v1.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2601-12.2012"},{"key":"2025111716300643000_2025.11.13.688363v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00088-6"},{"key":"2025111716300643000_2025.11.13.688363v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2919-09.2009"},{"key":"2025111716300643000_2025.11.13.688363v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/165.4.1805"},{"key":"2025111716300643000_2025.11.13.688363v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81141-1"},{"key":"2025111716300643000_2025.11.13.688363v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(88)80017-5"},{"key":"2025111716300643000_2025.11.13.688363v1.7","doi-asserted-by":"publisher","DOI":"10.1385\/1592590381"},{"key":"2025111716300643000_2025.11.13.688363v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007896"},{"key":"2025111716300643000_2025.11.13.688363v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80123-3"},{"key":"2025111716300643000_2025.11.13.688363v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.07.064"},{"key":"2025111716300643000_2025.11.13.688363v1.11","doi-asserted-by":"crossref","first-page":"110429","DOI":"10.1016\/j.jbc.2025.110429","article-title":"Genetic variants linked to neurodevelopmental disorders within the \u03b23-\u03b24 loop of the TRIO PH2 domain release autoinhibition of GEF2 activity","volume":"301","year":"2025","journal-title":"J Biol Chem"},{"key":"2025111716300643000_2025.11.13.688363v1.12","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/j.1460-2075.1989.tb03477.x","article-title":"The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells","volume":"8","year":"1989","journal-title":"EMBO J"},{"key":"2025111716300643000_2025.11.13.688363v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(04)89018-9"},{"key":"2025111716300643000_2025.11.13.688363v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1467-5"},{"key":"2025111716300643000_2025.11.13.688363v1.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3896-12.2013"},{"key":"2025111716300643000_2025.11.13.688363v1.16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21126"},{"key":"2025111716300643000_2025.11.13.688363v1.17","first-page":"121","article-title":"The \u2018window\u2019 T-type calcium current in brain dynamics of different behavioural states","volume":"562","year":"2004","journal-title":"The Journal of Physiology"},{"key":"2025111716300643000_2025.11.13.688363v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.012"},{"key":"2025111716300643000_2025.11.13.688363v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5466"},{"key":"2025111716300643000_2025.11.13.688363v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/336638a0"},{"key":"2025111716300643000_2025.11.13.688363v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyac084"},{"key":"2025111716300643000_2025.11.13.688363v1.22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7764"},{"key":"2025111716300643000_2025.11.13.688363v1.23","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-9-61"},{"key":"2025111716300643000_2025.11.13.688363v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02742-y"},{"key":"2025111716300643000_2025.11.13.688363v1.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210792200"},{"key":"2025111716300643000_2025.11.13.688363v1.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600179113"},{"key":"2025111716300643000_2025.11.13.688363v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601458"},{"key":"2025111716300643000_2025.11.13.688363v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/16711"},{"key":"2025111716300643000_2025.11.13.688363v1.29","doi-asserted-by":"crossref","first-page":"RP103620","DOI":"10.7554\/eLife.103620.3","article-title":"Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice","volume":"13","year":"2025","journal-title":"Elife"},{"key":"2025111716300643000_2025.11.13.688363v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00539.x"},{"key":"2025111716300643000_2025.11.13.688363v1.31","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.7.1391"},{"key":"2025111716300643000_2025.11.13.688363v1.32","unstructured":"Jose, A. and Collins, K . (2024). NALCN Channels Are Not Major targets of G\u03b1o or G\u03b1q Modulation in the C. elegans Egg-Laying Behavior Circuit. microPublication Biology."},{"key":"2025111716300643000_2025.11.13.688363v1.33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409460200"},{"key":"2025111716300643000_2025.11.13.688363v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.06.024"},{"key":"2025111716300643000_2025.11.13.688363v1.35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81505"},{"key":"2025111716300643000_2025.11.13.688363v1.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212287200"},{"key":"2025111716300643000_2025.11.13.688363v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80998-8"},{"key":"2025111716300643000_2025.11.13.688363v1.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2150-20.2021"},{"key":"2025111716300643000_2025.11.13.688363v1.39","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkab167"},{"key":"2025111716300643000_2025.11.13.688363v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80848-X"},{"key":"2025111716300643000_2025.11.13.688363v1.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.49.29051"},{"key":"2025111716300643000_2025.11.13.688363v1.42","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-11-92"},{"key":"2025111716300643000_2025.11.13.688363v1.43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00378"},{"key":"2025111716300643000_2025.11.13.688363v1.44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15271"},{"key":"2025111716300643000_2025.11.13.688363v1.45","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00574.x"},{"key":"2025111716300643000_2025.11.13.688363v1.46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017265"},{"key":"2025111716300643000_2025.11.13.688363v1.47","doi-asserted-by":"publisher","DOI":"10.1101\/gad.359706"},{"key":"2025111716300643000_2025.11.13.688363v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.05.008"},{"key":"2025111716300643000_2025.11.13.688363v1.49","doi-asserted-by":"crossref","first-page":"jeb250132","DOI":"10.1242\/jeb.250132","article-title":"Osmolarity regulates Caenorhabditis elegans egg-laying behavior via chemosensory and biophysical mechanisms","volume":"228","year":"2025","journal-title":"J Exp Biol"},{"key":"2025111716300643000_2025.11.13.688363v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80847-8"},{"key":"2025111716300643000_2025.11.13.688363v1.51","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E"},{"key":"2025111716300643000_2025.11.13.688363v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81232-5"},{"key":"2025111716300643000_2025.11.13.688363v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80835-1"},{"key":"2025111716300643000_2025.11.13.688363v1.54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2301-22.2023"},{"key":"2025111716300643000_2025.11.13.688363v1.55","doi-asserted-by":"crossref","unstructured":"Ravi, B. , Nassar, L. M. , Kopchock, R. J. , Dhakal, P. , Scheetz, M. and Collins, K. M . (2018a). Ratiometric Calcium Imaging of Individual Neurons in Behaving Caenorhabditis Elegans. J Vis Exp.","DOI":"10.3791\/56911"},{"key":"2025111716300643000_2025.11.13.688363v1.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3658-17.2018"},{"key":"2025111716300643000_2025.11.13.688363v1.57","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab080"},{"key":"2025111716300643000_2025.11.13.688363v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/46072"},{"key":"2025111716300643000_2025.11.13.688363v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/14755"},{"key":"2025111716300643000_2025.11.13.688363v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2186"},{"key":"2025111716300643000_2025.11.13.688363v1.61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703458200"},{"key":"2025111716300643000_2025.11.13.688363v1.62","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119515"},{"key":"2025111716300643000_2025.11.13.688363v1.63","doi-asserted-by":"publisher","DOI":"10.1126\/science.7886454"},{"key":"2025111716300643000_2025.11.13.688363v1.64","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805038200"},{"key":"2025111716300643000_2025.11.13.688363v1.65","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846707"},{"key":"2025111716300643000_2025.11.13.688363v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81406-3"},{"key":"2025111716300643000_2025.11.13.688363v1.67","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0586-18.2018"},{"key":"2025111716300643000_2025.11.13.688363v1.68","unstructured":"Tanis, J. E . (2008). Analysis of mechanisms that regulate neurotransmitter release from a pair of motor neurons in Caenorhabditis elegans. ProQuest Dissertations and Theses."},{"key":"2025111716300643000_2025.11.13.688363v1.69","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.079780"},{"key":"2025111716300643000_2025.11.13.688363v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/350516a0"},{"key":"2025111716300643000_2025.11.13.688363v1.71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167535"},{"key":"2025111716300643000_2025.11.13.688363v1.72","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3148-20.2021"},{"key":"2025111716300643000_2025.11.13.688363v1.73","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.116.198820"},{"key":"2025111716300643000_2025.11.13.688363v1.74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007032"},{"key":"2025111716300643000_2025.11.13.688363v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80527-9"},{"key":"2025111716300643000_2025.11.13.688363v1.76","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.1.151"},{"key":"2025111716300643000_2025.11.13.688363v1.77","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502734200"},{"key":"2025111716300643000_2025.11.13.688363v1.78","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1986.0056"},{"key":"2025111716300643000_2025.11.13.688363v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6540"},{"key":"2025111716300643000_2025.11.13.688363v1.80","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1592007"},{"key":"2025111716300643000_2025.11.13.688363v1.81","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060055"},{"key":"2025111716300643000_2025.11.13.688363v1.82","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22771"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.11.13.688363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:01:49Z","timestamp":1768471309000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.11.13.688363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":82,"URL":"https:\/\/doi.org\/10.1101\/2025.11.13.688363","relation":{},"subject":[],"published":{"date-parts":[[2025,11,14]]},"subtype":"preprint"}}