{"doi":"10.1101/2023.09.14.557804","title":"Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism","abstract":"TMEM106B is an endolysosomal transmembrane protein not only associated with multiple neurological disorders including frontotemporal dementia, Alzheimer's disease, and hypomyelinating leukodystrophy but also potentially involved in COVID-19. Additionally, recent studies have identified amyloid fibrils of C-terminal TMEM106B in both aged healthy and neurodegenerative brains. However, so far little is known about physiological functions of TMEM106B in the endolysosome and how TMEM106B is involved in a wide range of human conditions at molecular levels. Here, we performed lipidomic analysis of the brain of TMEM106B-deficient mice. We found that TMEM106B deficiency significantly decreases levels of two major classes of myelin lipids, galactosylceramide and its sulfated derivative sulfatide. Subsequent co-immunoprecipitation assay showed that TMEM106B physically interacts with galactosylceramidase. We also found that galactosyceramidase activity was significantly increased in TMEM106B-deficient brains. Thus, our results reveal a novel function of TMEM106B interacting with galactosyceramidase to regulate myelin lipid metabolism and have implications for TMEM106B-associated diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400756,"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":0.9524,"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":1177182,"name":"Azucena Pérez‐Cañamás","orcid":"0000-0003-3635-6298","position":1,"is_corresponding":false},{"id":1177486,"name":"Hongping Ye","orcid":null,"position":2,"is_corresponding":false},{"id":232153,"name":"Xianlin Han","orcid":"0000-0002-8615-2413","position":3,"is_corresponding":false},{"id":326241,"name":"Stephen M. Strittmatter","orcid":"0000-0001-8188-3092","position":4,"is_corresponding":false},{"id":618832,"name":"Hideyuki Takahashi","orcid":"0009-0004-4969-977X","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":"37745346","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":[]}