{"doi":"10.1021/acs.jproteome.3c00788","title":"Endogenous Protein–Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex","abstract":"NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein–protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein–protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1 I1061T ) while filtering out any protein interactor identified in the Npc1 –/– mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1 I1061T . Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1 I1061T . Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.","journal":"Journal of Proteome Research","year":2024,"id":476717,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"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":576902,"name":"Thu T. A. Nguyen","orcid":"0000-0001-8617-3305","position":1,"is_corresponding":false},{"id":662023,"name":"Ruth D. Azaria","orcid":"0000-0002-1686-2591","position":2,"is_corresponding":false},{"id":824179,"name":"Wenping Li","orcid":"0000-0001-5917-5380","position":3,"is_corresponding":false},{"id":821131,"name":"Daisy Edmison","orcid":null,"position":4,"is_corresponding":false},{"id":824181,"name":"Liang‐Wei Gong","orcid":"0000-0002-5868-6039","position":5,"is_corresponding":false},{"id":421638,"name":"Swetha Gowrishankar","orcid":"0000-0002-3043-8703","position":6,"is_corresponding":false},{"id":331941,"name":"Andrew P. Lieberman","orcid":"0000-0001-9032-580X","position":7,"is_corresponding":false},{"id":331938,"name":"Mark L. Schultz","orcid":"0000-0002-3149-4424","position":8,"is_corresponding":false},{"id":421639,"name":"Stephanie M. Cologna","orcid":"0000-0002-3541-3361","position":9,"is_corresponding":false},{"id":1314225,"name":"Roshan Javanshad","orcid":"0000-0001-8915-9285","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:06:29.605760Z","pmid":"38686625","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":[]}