{"doi":"10.1101/2022.05.25.493445","title":"De novo mapping of the apicomplexan Ca <sup>2+</sup> -responsive proteome","abstract":"ABSTRACT Apicomplexan parasites cause persistent mortality and morbidity worldwide through diseases including malaria, toxoplasmosis, and cryptosporidiosis. Ca 2+ signaling pathways have been repurposed in these eukaryotic pathogens to regulate parasite-specific cellular processes governing the transition between the replicative and lytic phases of the infectious cycle. Despite the presence of conserved Ca 2+ -responsive proteins, little is known about how specific signaling elements interact to impact pathogenesis. We mapped the Ca 2+ -responsive proteome of the model apicomplexan T. gondii via time-resolved phosphoproteomics and thermal proteome profiling. The waves of phosphoregulation following PKG activation and stimulated Ca 2+ release corroborate known physiological changes but identify specific proteins operating in these pathways. Thermal profiling of parasite extracts identified many expected Ca 2+ -responsive proteins, such as parasite Ca 2+ -dependent protein kinases. Our approach also identified numerous Ca 2+ -responsive proteins that are not predicted to bind Ca 2+ , yet are critical components of the parasite signaling network. We characterized protein phosphatase 1 (PP 1 ) as a Ca 2+ -responsive enzyme that relocalized to the parasite apex upon Ca 2+ store release. Conditional depletion of PP 1 revealed that the phosphatase regulates Ca 2+ uptake to promote parasite motility. PP 1 may thus be partly responsible for Ca 2+ -regulated serine/threonine phosphatase activity in apicomplexan parasites.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":308955,"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":0.9448,"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":480885,"name":"Zhu‐Hong Li","orcid":"0000-0003-4940-0729","position":1,"is_corresponding":false},{"id":752472,"name":"Alex W Chan","orcid":"0000-0002-5444-5756","position":2,"is_corresponding":false},{"id":480891,"name":"Silvia N.J. Moreno","orcid":"0000-0002-2041-6295","position":3,"is_corresponding":false},{"id":236241,"name":"Sebastian Lourido","orcid":"0000-0002-5237-1095","position":4,"is_corresponding":false},{"id":301618,"name":"Alice L Herneisen","orcid":"0000-0003-3368-0893","position":0,"is_corresponding":true}],"reference_count":147,"raw_metadata":null,"created_at":"2026-07-19T00:33:07.132912Z","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":[]}