{"doi":"10.33594/000000823","title":"Identification of Novel Kv1.3 Channel-Interacting Proteins Using Proximity Labelling in T-Cells","abstract":"BACKGROUND/AIMS: Potassium channels regulate membrane potential, calcium flux, cellular activation and effector functions of adaptive and innate immune cells. The voltage-activated Kv1.3 channel is an important regulator of T cell-mediated autoimmunity and microglia-mediated neuroinflammation. Kv1.3 channels, via protein-protein interactions, are localized with key immune proteins and pathways, enabling functional coupling between K+ efflux and immune mechanisms. METHODS: To gain insights into proteins and pathways that interact with Kv1.3 channels, we applied a proximity-labeling proteomics approach to characterize protein interactors of the Kv1.3 channel in activated T-cells. Biotin ligase TurboID was fused to either N or C termini of Kv1.3, stably expressed in Jurkat T cells, and biotinylated proteins in proximity to Kv1.3 were enriched and quantified by mass spectrometry. RESULTS: We identified over 1,800 Kv1.3 interactors including known interactors (beta-integrins, Stat1), although the majority were novel. We found that the N-terminus of Kv1.3 preferentially interacts with protein synthesis and protein trafficking machinery, while the C-terminus interacts with immune signaling and cell junction proteins. T-cell Kv1.3 interactors we found consisted of 335 cell surface proteins, including T-cell receptor complex, mitochondrial, calcium and cytokine-mediated signaling pathway, and lymphocyte migration proteins. 178 Kv1.3 interactors in T-cells also represent genetic risk factors for T cell-mediated autoimmunity, including STIM1, which was further validated using co-immunoprecipitation. CONCLUSION: Our studies revealed novel proteins and molecular pathways that interact with Kv1.3 channels in adaptive (T-cell) and innate (microglia) immune cells, providing a foundation for understanding how Kv1.3 channels may regulate immune mechanisms in autoimmune.","journal":"Cellular Physiology and Biochemistry","year":2025,"id":524749,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.973,"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":493945,"name":"Christine A Bowen","orcid":"0000-0002-2981-8629","position":1,"is_corresponding":false},{"id":1294968,"name":"Upasna Srivastava","orcid":"0000-0003-4096-9257","position":2,"is_corresponding":false},{"id":273474,"name":"Hai M. Nguyen","orcid":"0000-0002-1422-7041","position":3,"is_corresponding":false},{"id":1016652,"name":"Rashmi Kumari","orcid":"0000-0002-6654-855X","position":4,"is_corresponding":false},{"id":847988,"name":"Prateek Kumar","orcid":"0000-0001-5875-4065","position":5,"is_corresponding":false},{"id":1398829,"name":"Amanda Dabdab Brandelli","orcid":"0000-0003-0815-8008","position":6,"is_corresponding":false},{"id":1041490,"name":"Sara Bitarafan","orcid":"0000-0003-4584-1420","position":7,"is_corresponding":false},{"id":1187058,"name":"Brendan Tobin","orcid":"0000-0003-1250-4356","position":8,"is_corresponding":false},{"id":284965,"name":"Levi B. Wood","orcid":"0000-0002-4248-0888","position":9,"is_corresponding":false},{"id":21539,"name":"Nicholas T. Seyfried","orcid":"0000-0002-4507-624X","position":10,"is_corresponding":false},{"id":227732,"name":"Heike Wulff","orcid":"0000-0003-4437-5763","position":11,"is_corresponding":false},{"id":107093,"name":"Srikant Rangaraju","orcid":"0000-0003-2765-1500","position":12,"is_corresponding":false},{"id":1398828,"name":"Dilpreet Kour","orcid":"0009-0006-4865-2376","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41277224","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":[]}