{"doi":"10.1101/2021.07.27.453988","title":"A phospho-switch at Acinus-Serine <sup>437</sup> controls autophagic responses to Cadmium exposure and neurodegenerative stress","abstract":"Summary Neuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in Drosophila starvation-independent quality control autophagy is regulated by Acinus and the Cdk5-dependent phosphorylation of its serine 437 (Nandi et al., 2017). Here, we identify the phosphatase that counterbalances this activity and provides for the dynamic nature of Acinus-S437 phosphorylation. A genetic screen identified six phosphatases that genetically interacted with an Acinus gain-of-function model. Among these, loss of function of only one, the PPM-type phosphatase Nil (CG6036), enhanced pS437-Acinus levels. Cdk5-dependent phosphorylation of Acinus serine 437 in nil 1 animals elevates neuronal autophagy and reduces the accumulation of polyQ proteins in a Drosophila Huntington’s disease model. Consistent with previous findings that Cd 2+ inhibits PPM-type phosphatases, Cd 2+ -exposure elevated Acinus-serine 437 phosphorylation which was necessary for increased neuronal autophagy and protection against Cd 2+ -induced cytotoxicity. Together, our data establish the Acinus- S437 phospho-switch as critical integrator of multiple stress signals regulating neuronal autophagy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225805,"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":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":828907,"name":"Zuhair Zaidi","orcid":null,"position":1,"is_corresponding":false},{"id":501746,"name":"Charles Tracy","orcid":"0000-0001-7769-4950","position":2,"is_corresponding":false},{"id":501747,"name":"Helmut Krämer","orcid":"0000-0002-1167-2676","position":3,"is_corresponding":false},{"id":501745,"name":"Nilay Nandi","orcid":"0000-0002-7088-4943","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:30.292454Z","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":[]}