{"doi":"10.1016/j.celrep.2020.02.064","title":"APOL1 C-Terminal Variants May Trigger Kidney Disease through Interference with APOL3 Control of Actomyosin","abstract":"The C-terminal variants G1 and G2 of apolipoprotein L1 (APOL1) confer human resistance to the sleeping sickness parasite Trypanosoma rhodesiense , but they also increase the risk of kidney disease. APOL1 and APOL3 are death-promoting proteins that are partially associated with the endoplasmic reticulum and Golgi membranes. We report that in podocytes, either APOL1 C-terminal helix truncation (APOL1Δ) or APOL3 deletion (APOL3KO) induces similar actomyosin reorganization linked to the inhibition of phosphatidylinositol-4-phosphate [PI(4)P] synthesis by the Golgi PI(4)-kinase IIIB (PI4KB). Both APOL1 and APOL3 can form K + channels, but only APOL3 exhibits Ca 2+ -dependent binding of high affinity to neuronal calcium sensor-1 (NCS-1), promoting NCS-1-PI4KB interaction and stimulating PI4KB activity. Alteration of the APOL1 C-terminal helix triggers APOL1 unfolding and increased binding to APOL3, affecting APOL3-NCS-1 interaction. Since the podocytes of G1 and G2 patients exhibit an APOL1Δ or APOL3KO-like phenotype, APOL1 C-terminal variants may induce kidney disease by preventing APOL3 from activating PI4KB, with consecutive actomyosin reorganization of podocytes.","journal":"Cell Reports","year":2020,"id":57586,"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":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":301139,"name":"Laurence Lecordier","orcid":"0000-0003-0604-5819","position":1,"is_corresponding":false},{"id":303134,"name":"Pierrick Uzureau","orcid":null,"position":2,"is_corresponding":false},{"id":301140,"name":"Dorle Hennig","orcid":"0000-0002-3167-5524","position":3,"is_corresponding":false},{"id":301141,"name":"Jonas Heilskov Graversen","orcid":"0000-0001-7119-2108","position":4,"is_corresponding":false},{"id":301142,"name":"Fabrice Homblé","orcid":"0000-0001-6031-136X","position":5,"is_corresponding":false},{"id":303135,"name":"Pepe Ekulu Mfutu","orcid":null,"position":6,"is_corresponding":false},{"id":301143,"name":"Fanny Oliveira Arcolino","orcid":"0000-0003-2207-9699","position":7,"is_corresponding":false},{"id":303136,"name":"Ana Raquel Ramos","orcid":null,"position":8,"is_corresponding":false},{"id":303137,"name":"Rita M. 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