{"doi":"10.1101/2025.02.09.637126","title":"Calcium channel-coupled transcription factors facilitate direct nuclear signaling","abstract":"Summary VGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity- dependent neuronal development, and forming long-term memory by regulating Ca 2+ 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 Ca 2+ - 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 Ca 2+ -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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":561817,"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":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":814630,"name":"Tyler Thaxton","orcid":"0000-0002-9901-7771","position":1,"is_corresponding":false},{"id":1464313,"name":"Eric Gama","orcid":null,"position":2,"is_corresponding":false},{"id":963516,"name":"Jack D. Godfrey","orcid":"0000-0001-5962-3411","position":3,"is_corresponding":false},{"id":963518,"name":"Cenfu Wei","orcid":"0000-0003-3368-4974","position":4,"is_corresponding":false},{"id":1171908,"name":"Qiaoshan Lin","orcid":"0000-0001-7851-6048","position":5,"is_corresponding":false},{"id":1464027,"name":"Yan Li","orcid":"0000-0002-8941-1070","position":6,"is_corresponding":false},{"id":1412537,"name":"Daniel Parviz Hejazi Pastor","orcid":"0000-0002-7173-5384","position":7,"is_corresponding":false},{"id":393603,"name":"Christian Hansel","orcid":"0000-0001-5750-7097","position":8,"is_corresponding":false},{"id":1464028,"name":"Xiaofei Du","orcid":"0000-0001-6747-2860","position":9,"is_corresponding":false},{"id":1464029,"name":"Christopher Gomez","orcid":"0000-0002-6612-9646","position":10,"is_corresponding":false},{"id":963925,"name":"Eshaan Rao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39990342","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":[]}