{"doi":"10.3389/fcell.2023.1240285","title":"Native lamin A/C proteomes and novel partners from heart and skeletal muscle in a mouse chronic inflammation model of human frailty","abstract":"Clinical frailty affects ∼10% of people over age 65 and is studied in a chronically inflamed (Interleukin-10 knockout; “IL10-KO”) mouse model. Frailty phenotypes overlap the spectrum of diseases (“laminopathies”) caused by mutations in LMNA . LMNA encodes nuclear intermediate filament proteins lamin A and lamin C (“lamin A/C”), important for tissue-specific signaling, metabolism and chromatin regulation. We hypothesized that wildtype lamin A/C associations with tissue-specific partners are perturbed by chronic inflammation, potentially contributing to dysfunction in frailty. To test this idea we immunoprecipitated native lamin A/C and associated proteins from skeletal muscle, hearts and brains of old (21–22 months) IL10-KO versus control C57Bl/6 female mice, and labeled with Tandem Mass Tags for identification and quantitation by mass spectrometry. We identified 502 candidate lamin-binding proteins from skeletal muscle, and 340 from heart, including 62 proteins identified in both tissues. Candidates included frailty phenotype-relevant proteins Perm1 and Fam210a, and nuclear membrane protein Tmem38a, required for muscle-specific genome organization. These and most other candidates were unaffected by IL10-KO, but still important as potential lamin A/C-binding proteins in native heart or muscle. A subset of candidates (21 in skeletal muscle, 30 in heart) showed significantly different lamin A/C-association in an IL10-KO tissue ( p < 0.05), including AldoA and Gins3 affected in heart, and Lmcd1 and Fabp4 affected in skeletal muscle. To screen for binding, eleven candidates plus prelamin A and emerin controls were arrayed as synthetic 20-mer peptides (7-residue stagger) and incubated with recombinant purified lamin A “tail” residues 385–646 under relatively stringent conditions. We detected strong lamin A binding to peptides solvent exposed in Lmcd1, AldoA, Perm1, and Tmem38a, and plausible binding to Csrp3 (muscle LIM protein). These results validated both proteomes as sources for native lamin A/C-binding proteins in heart and muscle, identified four candidate genes for Emery-Dreifuss muscular dystrophy (CSRP3, LMCD1, ALDOA, and PERM1), support a lamin A-interactive molecular role for Tmem38A, and supported the hypothesis that lamin A/C interactions with at least two partners (AldoA in heart, transcription factor Lmcd1 in muscle) are altered in the IL10-KO model of frailty.","journal":"Frontiers in Cell and Developmental Biology","year":2023,"id":373664,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1135374,"name":"Arushi Samal","orcid":null,"position":1,"is_corresponding":false},{"id":616060,"name":"Adith S. Arun","orcid":"0000-0003-3675-9521","position":2,"is_corresponding":false},{"id":867874,"name":"Tejas Dharmaraj","orcid":"0000-0002-5305-9968","position":3,"is_corresponding":false},{"id":1135375,"name":"Neeti R. Prasad","orcid":null,"position":4,"is_corresponding":false},{"id":1135376,"name":"Alex Rendon-Jonguitud","orcid":null,"position":5,"is_corresponding":false},{"id":400541,"name":"Lauren DeVine","orcid":"0000-0002-9838-0704","position":6,"is_corresponding":false},{"id":57359,"name":"Jeremy Walston","orcid":"0000-0002-6965-2723","position":7,"is_corresponding":false},{"id":299276,"name":"Robert N. Cole","orcid":"0000-0002-3096-4754","position":8,"is_corresponding":false},{"id":731118,"name":"Katherine L. Wilson","orcid":"0000-0003-1402-4735","position":9,"is_corresponding":false},{"id":1135373,"name":"Fatima D. Elzamzami","orcid":null,"position":0,"is_corresponding":true}],"reference_count":142,"raw_metadata":null,"created_at":"2026-07-19T01:16:07.080027Z","pmid":"37936983","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":[]}