Chemoreceptor TRPγ coordinates locomotor activity via regulating intracellular Ca2+ homeostasis in Drosophila

Chemoreceptor TRPγ coordinates locomotor activity via regulating intracellular Ca2+ homeostasis in Drosophila | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Chemoreceptor TRPγ coordinates locomotor activity via regulating intracellular Ca 2+ homeostasis in Drosophila Jing Yao, Peiyuan Pang, Bomin Gao, Xiaoyi Mo, Xuteng Lu, Xiang Li, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7403702/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Chemosensation underlies animal behavioral adaptation in ever-changing environments. As a member of the canonical transient receptor potential (TRP), TRPγ orchestrates the chemosensation and the adaptive behavior via fine motor control in Drosophila. Yet, how TRPγ senses and transduces chemical cues has been elusive. Here, we explored cryo-EM structures of dTRPγ in both apo and camphor-bound states, with resolutions of 2.18 Å and 3.44 Å, respectively, thereby capturing ligand-induced pore dilation. Through analysis of dTRPγchannel structure, we further identified two allosteric Ca2+-sensing modules: an activating site embedded within the voltage-sensor-like domain (VSLD) and an inhibitory site coordinated by the intracellular ankyrin repeat domain (ARD) and coiled-coil domain (CCD). These spatially segregated sensors convert cytoplasmic Ca2+ into opposing gating signals, maintaining calcium homeostasis via a dual-feedback manner. In vivo, this bidirectional regulation directly controls locomotor kinematics by modulating stride length and velocity, while mutants with lost Ca2+ regulatory functions exhibit impaired locomotor activity. Together, our findings reveal that dTRPγ acts as an independent ion channel, integrating environmental cues with ionic dynamics to drive adaptive behavior. Biological sciences/Chemical biology/Ion channels/Transient receptor potential channels Biological sciences/Structural biology/Electron microscopy/Cryoelectron microscopy TRPγ Cryo-EM Calcium Chemoreception Locomotion Full Text Additional Declarations There is NO Competing Interest. Supplementary Files DescriptionofAdditionalSupplementaryFiles.pdf Descriptions of Supplementary Movie 1 and 2 PDBValidationReportsYao20250819.pdf PDB Validation Reports SupplementaryInformation.pdf Supplementary Information SupplementaryMovie1.mp4 Supplementary Movie 1 SupplementaryMovie2.mp4 Supplementary Movie 2 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7403702","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":507612601,"identity":"3db18ffd-ec44-44d1-aca5-7d7939927612","order_by":0,"name":"Jing 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