{"doi":"10.1101/2023.09.22.558856","title":"A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings","abstract":"Abstract L-type Ca 2+ channels (Ca V 1.2/1.3) convey influx of calcium ions (Ca 2+ ) that orchestrate a bevy of biological responses including muscle contraction and gene transcription. Deficits in Ca V 1 function play a vital role in cardiac and neurodevelopmental disorders. Yet conventional pharmacological approaches to upregulate Ca V 1 are limited, as excessive Ca 2+ influx leads to cytotoxicity. Here, we develop a genetically encoded enhancer of Ca V 1.2/1.3 channels (GeeC) to manipulate Ca 2+ entry in distinct physiological settings. Specifically, we functionalized a nanobody that targets the Ca V macromolecular complex by attaching a minimal effector domain from a Ca V enhancer—leucine rich repeat containing protein 10 (Lrrc10). In cardiomyocytes, GeeC evoked a 3-fold increase in L-type current amplitude. In neurons, GeeC augmented excitation-transcription (E-T) coupling. In all, GeeC represents a powerful strategy to boost Ca V 1.2/1.3 function in distinct physiological settings and, in so doing, lays the groundwork to illuminate new insights on neuronal and cardiac physiology and disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400869,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1177992,"name":"Diego Scala Chavez","orcid":null,"position":1,"is_corresponding":false},{"id":929303,"name":"Srinidhi Jayaraman","orcid":null,"position":2,"is_corresponding":false},{"id":1177575,"name":"Lin Yang","orcid":"0000-0002-9206-791X","position":3,"is_corresponding":false},{"id":1143856,"name":"Audrey Lauris Kochiss","orcid":"0009-0007-4800-9855","position":4,"is_corresponding":false},{"id":395048,"name":"Henry M. Colecraft","orcid":"0000-0002-2340-8899","position":5,"is_corresponding":false},{"id":245806,"name":"X. Shawn Liu","orcid":"0000-0002-2799-2519","position":6,"is_corresponding":false},{"id":484279,"name":"Steven O. Marx","orcid":"0000-0002-0577-6030","position":7,"is_corresponding":false},{"id":344892,"name":"Anjali M. Rajadhyaksha","orcid":"0000-0002-8399-5466","position":8,"is_corresponding":false},{"id":484278,"name":"Manu Ben‐Johny","orcid":"0000-0002-5645-0815","position":9,"is_corresponding":false},{"id":1143855,"name":"Pedro J. del Rivero Morfin","orcid":"0000-0002-8554-145X","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37790372","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":[]}