{"doi":"10.7554/elife.103870","title":"Flower/FLWR-1 regulates neuronal activity via the plasma membrane Ca2+ ATPase to promote recycling of synaptic vesicles","abstract":"The Flower protein was suggested to couple the fusion of synaptic vesicles (SVs) to their recycling in different model organisms. It is supposed to trigger activity-dependent bulk endocytosis by conducting Ca 2+ at endocytic sites. However, this mode of action is debated. Here, we investigated the role of the Caenorhabditis elegans homologue FLWR-1 in neurotransmission. Our results confirm that FLWR-1 facilitates the recycling of SVs at the neuromuscular junction (NMJ). Ultrastructural analysis of synaptic boutons after hyperstimulation revealed an accumulation of large endocytic structures in flwr-1 mutants. These findings do not support a role of FLWR-1 in the formation of bulk endosomes but rather a function in their breakdown. Unexpectedly, the loss of FLWR-1 led to increased neuronal Ca 2+ levels in axon terminals during stimulation, particularly in GABAergic motor neurons, causing excitation-inhibition imbalance. We found that this increased NMJ transmission might be caused by deregulation of MCA-3, the nematode orthologue of the plasma membrane Ca 2+ ATPase (PMCA). In vivo molecular interactions indicated that FLWR-1 may be a positive regulator of the PMCA and might influence its recycling through modification of plasma membrane levels of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ).","journal":"eLife","year":2024,"id":487549,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1277024,"name":"Jasmina Redzovic","orcid":null,"position":1,"is_corresponding":false},{"id":723552,"name":"Jana Liewald","orcid":"0000-0002-2050-0745","position":2,"is_corresponding":false},{"id":1276593,"name":"Dennis Rentsch","orcid":"0009-0006-9090-9016","position":3,"is_corresponding":false},{"id":1332272,"name":"Stepan Shapiguzov","orcid":null,"position":4,"is_corresponding":false},{"id":999003,"name":"Noah Schuh","orcid":null,"position":5,"is_corresponding":false},{"id":998565,"name":"Nils Rosenkranz","orcid":"0009-0002-2556-7276","position":6,"is_corresponding":false},{"id":1057882,"name":"Stefan Eimer","orcid":null,"position":7,"is_corresponding":false},{"id":349997,"name":"Alexander Gottschalk","orcid":"0000-0002-1197-6119","position":8,"is_corresponding":false},{"id":998564,"name":"Marius Seidenthal","orcid":"0009-0001-0563-7719","position":0,"is_corresponding":true}],"reference_count":125,"raw_metadata":null,"created_at":"2026-07-19T02:08:10.215754Z","pmid":"40392238","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":[]}