{"doi":"10.1101/2025.04.16.649205","title":"Multivalent assembly of PAR-3 / aPKC complexes establishes cell polarity in <i>C. elegans</i> zygotes","abstract":"Abstract Cell polarity is essential for the formation and function of animal tissues. Atypical protein kinase C (aPKC), its cofactor PAR-6, and scaffold protein PAR-3 regulate cell polarity in many different animal cell types. PAR-3 oligomerization is important to establish cell polarity, but how oligomerization relates to the assembly of the PAR-3 / aPKC / PAR-6 complex is still unclear. Here, we use in vivo and ex vivo single molecule techniques to demonstrate cooperativity between PAR-3 oligomerization and its binding to aPKC / PAR-6 in the C. elegans zygote. Using genetic perturbations, we demonstrate that aPKC and PAR-6 have independent binding sites for PAR-3. We propose that multivalency drives cooperativity because a single aPKC / PAR-6 heterodimer can interact simultaneously with multiple PAR-3 molecules in an oligomer. Although single binding site mutations do not fully eliminate PAR-3 / aPKC / PAR-6 binding, they do abolish anterior-posterior polarity, demonstrating that PAR-3 / aPKC cooperativity is essential for polarity establishment. Finally, PAR-3 / aPKC cooperativity is downregulated in polarity maintenance, and this downregulation depends on the mitotic kinase PLK-1. Together, our results show how cells can developmentally regulate multivalent assembly of a key polarity complex to achieve timely segregation of cell fate determinants.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":564673,"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":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":361111,"name":"Daniel J. Dickinson","orcid":"0000-0003-2651-2584","position":1,"is_corresponding":false},{"id":1467953,"name":"Sheng-Ping Hsu","orcid":"0000-0002-3169-7635","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:24.872312Z","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":[]}