{"doi":"10.1101/2022.03.30.486445","title":"Importin α/β Promote Kif18B Microtubule Association to Spatially Control Microtubule Destabilization","abstract":"Abstract Tight regulation of microtubule (MT) dynamics is necessary for proper spindle assembly and chromosome segregation. The MT destabilizing Kinesin-8, Kif18B, controls astral MT dynamics and spindle positioning. Kif18B interacts with importin α/β as well as with the plus-tip tracking protein EB1, but how these associations modulate Kif18B is not known. We mapped the key binding sites on Kif18B, made residue-specific mutations, and assessed their impact on Kif18B function. Blocking EB1 interaction disrupted Kif18B MT plus-end accumulation and inhibited its ability to control MT length on monopolar spindles in cells. Blocking importin α/β interaction disrupted Kif18B localization without affecting aster size. In vitro , importin α/β increased Kif18B MT association by increasing the on-rate and decreasing the off-rate from MTs, which stimulated MT destabilization. In contrast, EB1 promoted MT destabilization without increasing lattice binding in vitro , which suggests that EB1 and importin α/β have distinct roles in the regulation of Kif18B-mediated MT destabilization. We propose that importin α/β-spatially modulate Kif18B association with MTs to facilitate its MT destabilization activity. Our results suggest that Ran-regulation is important not only to control molecular motor function near chromatin but also provides a spatial control mechanism to modulate MT binding of NLS-containing spindle assembly factors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302874,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9628,"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":574462,"name":"Stephanie C. Ems-McClung","orcid":"0000-0001-5209-0739","position":1,"is_corresponding":false},{"id":575158,"name":"Mark Hazelbaker","orcid":null,"position":2,"is_corresponding":false},{"id":995273,"name":"Amber L. Yount","orcid":null,"position":3,"is_corresponding":false},{"id":468999,"name":"Sidney L. Shaw","orcid":"0000-0001-9195-6128","position":4,"is_corresponding":false},{"id":574463,"name":"Claire Walczak","orcid":"0000-0002-7378-2133","position":5,"is_corresponding":false},{"id":766265,"name":"Sanjay Shrestha","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:32:20.348385Z","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":[]}