Calcium channel-coupled transcription factors facilitate direct nuclear signaling

Calcium channel-coupled transcription factors facilitate direct nuclear signaling | 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 Article Calcium channel-coupled transcription factors facilitate direct nuclear signaling Christopher Gomez, Eshaan Rao, Tyler Thaxton, Eric Gama, Jack Godfrey, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6180510/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 VGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity-dependent neuronal development, and forming long-term memory by regulating Ca2+ influx. The intracellular carboxyl-terminal domains of VGCC α1 subunits help regulate VGCC function. Emerging evidence suggests that some VGCC C-termini have functions independent of channel gating and exist as stable proteins. Here, we demonstrate that all VGCC gene family members express bicistronic mRNA transcripts that produce functionally distinct C-terminal proteins (CTPs) in tandem with full-length VGCC α1 subunits. Two of these CTPs, α1CCT and α1ACT, cycle to and from the nucleus in a Ca2+- and calmodulin-dependent fashion. α1CCT, α1ACT, and α1HCT regulate chromatin accessibility and/or bind directly to genes, regulating gene networks involved in neuronal differentiation and synaptic function in a Ca2+-dependent manner. This study elucidates a conserved process of coordinated protein expression within the VGCC family, coupling the channel function with VGCC C-terminal transcription factors. Biological sciences/Neuroscience/Ion channels in the nervous system Biological sciences/Molecular biology/Transcriptomics Voltage-gated Ca2+ channels bicistronic cellular genes C-terminal proteins Ca2+ signaling neuronal differentiation synaptic function CACNA1A CACNA1C CACNA1H α1ACT α1CCT α1HCT VGCC Full Text Additional Declarations There is NO Competing Interest. Supplementary Files VideoS1EV1.wmv Video S1 Live cell imaging of EV-emGFP in cultured rat cortical neurons VideoS2a1CCT.wmv Video S2 Live cell imaging of α1CCT in cultured rat cortical neurons VideoS3a1ACT.wmv Video S3 Live cell imaging of α1ACT in cultured rat cortical neurons VideoS4a1HCT.wmv Video S4 Live cell imaging of α1HCT in cultured rat cortical neurons SupplementalDocuments.pdf Supplemental Documents 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. 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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-6180510","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":438174121,"identity":"bc482ab1-977a-4cfe-82bb-bca901e38e21","order_by":0,"name":"Christopher 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