{"doi":"10.1101/2024.11.26.625568","title":"Activation and regulation of the dynein-dynactin-NuMA complex","abstract":"During cell division, NuMA orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules, and other cellular factors. Here we used in vitro reconstitution, cryo-electron microscopy, and live cell imaging to understand the mechanism and regulation of NuMA. We determined the structure of the processive dynein/dynactin/NuMA complex (DDN) and showed that the NuMA N-terminus drives dynein motility in vitro and facilitates dynein-mediated transport in live cells. The C-terminus of NuMA directly binds to and suppresses the dynamics of the microtubule minus-end. Full-length NuMA is autoinhibited, but mitotically phosphorylated NuMA activates dynein in vitro and interphase cells. Together with dynein, activated full-length NuMA focuses microtubule minus-ends into aster-like structures. The binding of the cortical protein LGN to the NuMA C-terminus results in preferential binding of NuMA to the microtubule plus-end. These results provide critical insights into the activation of NuMA and dynein for their functions in the spindle body and the cell cortex.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484769,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":862041,"name":"Ennio d’Amico","orcid":"0000-0002-1451-6273","position":1,"is_corresponding":false},{"id":680131,"name":"Nathan Cho","orcid":"0000-0002-0110-1343","position":2,"is_corresponding":false},{"id":1326945,"name":"Aryan Taheri","orcid":"0000-0001-8050-8709","position":3,"is_corresponding":false},{"id":308991,"name":"Juan M. Perez-Bertoldi","orcid":"0000-0003-4590-820X","position":4,"is_corresponding":false},{"id":484399,"name":"Yuanchang Zhao","orcid":"0000-0003-1458-5321","position":5,"is_corresponding":false},{"id":1327404,"name":"Xinyue Zhong","orcid":null,"position":6,"is_corresponding":false},{"id":1327405,"name":"Madeline Blaauw","orcid":null,"position":7,"is_corresponding":false},{"id":1176853,"name":"Andrew P. Carter","orcid":"0000-0001-7292-5430","position":8,"is_corresponding":false},{"id":296314,"name":"Sophie Dumont","orcid":"0000-0002-8283-1523","position":9,"is_corresponding":false},{"id":281189,"name":"Ahmet Yıldız","orcid":"0000-0003-4792-174X","position":10,"is_corresponding":false},{"id":260482,"name":"Merve Aslan","orcid":"0000-0002-0115-3426","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:07:42.971417Z","pmid":"39651296","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":[]}