{"doi":"10.1101/2020.02.13.944967","title":"Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in <i>Caenorhabditis elegans</i>","abstract":"Abstract Molecular chaperones often work collaboratively with the ubiquitination-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of Caenorhabditis elegans , we find that mec-15(−) mutants display defects in microtubule formation, neurite growth, synaptic development, and neuronal functions, and these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and cochaperones. MEC-15 likely functions in a SCF complex to degrade DLK-1, which is an Hsp90 client protein stabilized by the chaperones. The abundance of DLK-1, and likely other Hsp90 substrates, is fine-tuned by the antagonism between MEC-15 and chaperones; this antagonism regulates TRN development as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between UPS and chaperones tightly controls neuronal differentiation. Summary statement Molecular chaperones are known to protect cells from stress. However, in this study the authors showed that the Hsp90 chaperone negatively regulates neuronal differentiation when the ubiquitination-proteasome system is compromised.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128932,"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":0.952,"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":416246,"name":"Emily G Atlas","orcid":"0000-0002-0705-6109","position":1,"is_corresponding":false},{"id":416247,"name":"Ho Ming Terence Lee","orcid":"0000-0003-3376-371X","position":2,"is_corresponding":false},{"id":417117,"name":"Susan Laura Javier Jao","orcid":null,"position":3,"is_corresponding":false},{"id":345354,"name":"Ken C. Q. Nguyen","orcid":"0000-0002-3479-2611","position":4,"is_corresponding":false},{"id":310868,"name":"David H. Hall","orcid":"0000-0001-8459-9820","position":5,"is_corresponding":false},{"id":29697,"name":"Martin Chalfie","orcid":"0000-0002-9079-7046","position":6,"is_corresponding":false},{"id":416245,"name":"Chaogu Zheng","orcid":"0000-0002-5048-4520","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","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":[]}