{"doi":"10.1101/2022.05.13.491370","title":"Vitamin K-dependent γ-carboxylation regulates calcium flux and adaptation to metabolic stress in β-cells","abstract":"SUMMARY Vitamin K is a micronutrient necessary for the γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Clinical studies have recently implicated vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse β-cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced β-cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identified Endoplasmic Reticulum Gla Protein (ERGP) as a novel γ-carboxylated ER-resident calcium-binding protein expressed in β-cells. Mechanistically, γ-carboxylation of ERGP protects cells against calcium overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated calcium entry. These results reveal a critical role for vitamin K-dependent γ-carboxylation in the regulation of calcium flux in β-cells and in their capacity to adapt to metabolic stress.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":308542,"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":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353757,"name":"Kevin Guo","orcid":"0000-0002-5893-2164","position":1,"is_corresponding":false},{"id":1003070,"name":"Jessica Bonneau","orcid":"0000-0002-6751-1150","position":2,"is_corresponding":false},{"id":582311,"name":"Denis Faubert","orcid":"0000-0001-9550-4495","position":3,"is_corresponding":false},{"id":1003404,"name":"Florian Gioanni","orcid":null,"position":4,"is_corresponding":false},{"id":828580,"name":"Alexis Vivoli","orcid":"0000-0002-6056-9632","position":5,"is_corresponding":false},{"id":1003071,"name":"Sarah M. Muir","orcid":"0000-0002-7082-7199","position":6,"is_corresponding":false},{"id":1003072,"name":"Soraya Hezzaz","orcid":"0009-0009-5984-2767","position":7,"is_corresponding":false},{"id":576873,"name":"Vincent Poitout","orcid":"0000-0002-6555-5053","position":8,"is_corresponding":false},{"id":497947,"name":"Mathieu Ferron","orcid":"0000-0002-5858-2686","position":9,"is_corresponding":false},{"id":1003069,"name":"Julie Lacombe","orcid":"0000-0002-1046-9908","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:03.486542Z","pmid":null,"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":[]}