{"doi":"10.1101/2025.09.01.673543","title":"A-type lamins anchor emerin at the inner nuclear membrane via two independent binding sites","abstract":"Lamins form a dense meshwork at the inner surface of the inner nuclear membrane (INM), where they interact with other nuclear envelope proteins such as emerin. Emerin is an integral membrane protein that is part of the LEM (LAP2/emerin/MAN1) domain family, and mutations in either emerin or lamin A/C can result in Emery-Dreifuss muscular dystrophy (EDMD) and other striated muscle diseases. Emerin is retained at the INM through direct interaction with lamin A/C, and emerin's proper subcellular localization is critical for its ability to influence the mechanical properties of the nucleus and participate in various signaling processes. Nonetheless, the requirements for interaction between emerin and lamin A/C at the INM remain incompletely understood. Here, we report that two distinct regions of lamin A/C are each sufficient to properly localize emerin to the INM and prevent emerin's lateral diffusion within the INM. In addition to a previously described region of the lamin A/C tail domain able to bind emerin, we identify a novel emerin-interacting domain comprising the linker between the rod and Ig-like fold domains of lamin A/C. We further demonstrate that stably anchoring emerin to the INM requires assembly of A-type lamins into a filamentous network. Collectively, our findings suggest a revised model for emerin retention at the INM, which predicts that two independent lamin A/C domains are required to retain emerin at the nuclear envelope, thereby illuminating how diverse mutations in lamin A/C result in EDMD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":573979,"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":0.948,"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":1481495,"name":"Kristen Nedza","orcid":null,"position":1,"is_corresponding":false},{"id":244548,"name":"Jan Lammerding","orcid":"0000-0003-4335-8611","position":2,"is_corresponding":false},{"id":1053707,"name":"Jacob Odell","orcid":"0000-0001-9043-1338","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40950172","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":[]}