{"doi":"10.1038/ncomms1735","title":"Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release","abstract":null,"journal":"Nature Communications","year":2012,"id":689234,"datarank":9.823619848123936,"base_score":6.214608098422191,"endowment":6.214608098422191,"self_citation_contribution":0.9321912147633289,"citation_network_contribution":8.891428633360608,"self_endowment_contribution":0.9321912147633289,"citer_contribution":8.891428633360608,"corpus_percentile":null,"corpus_rank":null,"citation_count":499,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1459670,"name":"Xiang Wang","orcid":"0000-0002-1522-9532","position":1,"is_corresponding":false},{"id":1174099,"name":"Xinran Li","orcid":"0000-0001-8988-7223","position":2,"is_corresponding":false},{"id":386160,"name":"Xiaoli Zhang","orcid":"0000-0002-2495-4568","position":3,"is_corresponding":false},{"id":816825,"name":"Zepeng Yao","orcid":"0000-0002-0186-5503","position":4,"is_corresponding":false},{"id":1800590,"name":"Shannon Dibble","orcid":null,"position":5,"is_corresponding":false},{"id":1800591,"name":"Xian-ping Dong","orcid":null,"position":6,"is_corresponding":false},{"id":15688,"name":"Ting Yu","orcid":"0000-0003-4096-8975","position":7,"is_corresponding":false},{"id":331941,"name":"Andrew P. Lieberman","orcid":"0000-0001-9032-580X","position":8,"is_corresponding":false},{"id":536704,"name":"Hollis D. Showalter","orcid":"0000-0003-2863-0170","position":9,"is_corresponding":false},{"id":254906,"name":"Haoxing Xu","orcid":"0000-0003-3561-4654","position":10,"is_corresponding":false},{"id":1800589,"name":"Dongbiao Shen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release","abstract":"Lysosomal lipid accumulation, defects in membrane trafficking and altered Ca(2+) homoeostasis are common features in many lysosomal storage diseases. Mucolipin transient receptor potential channel 1 (TRPML1) is the principle Ca(2+) channel in the lysosome. Here we show that TRPML1-mediated lysosomal Ca(2+) release, measured using a genetically encoded Ca(2+) indicator (GCaMP3) attached directly to TRPML1 and elicited by a potent membrane-permeable synthetic agonist, is dramatically reduced in Niemann-Pick (NP) disease cells. Sphingomyelins (SMs) are plasma membrane lipids that undergo sphingomyelinase (SMase)-mediated hydrolysis in the lysosomes of normal cells, but accumulate distinctively in lysosomes of NP cells. Patch-clamp analyses revealed that TRPML1 channel activity is inhibited by SMs, but potentiated by SMases. In NP-type C cells, increasing TRPML1's expression or activity was sufficient to correct the trafficking defects and reduce lysosome storage and cholesterol accumulation. We propose that abnormal accumulation of luminal lipids causes secondary lysosome storage by blocking TRPML1- and Ca(2+)-dependent lysosomal trafficking.","is_dataset_classified":null,"base_score":6.214608098422191,"endowment":6.214608098422191,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22415822","pmcid":"PMC3347486","openalex_id":"https://openalex.org/W2065773869","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS062792","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS063967","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS062792","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS063967","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R03 MH096595","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institutes of Health","grant_id":"5R01NS063967-05","title":"Unraveling mechanisms of Niemann-Pick C neuropathology with mouse models"},{"funder_name":"National Institutes of Health","grant_id":"2R01NS062792-08","title":"The Mucolipin TRP Ion Channels"}],"total_grants":8,"fwci":19.4826,"citation_percentile":0.9976102,"influential_citations":38,"citation_trend":[{"year":2012,"count":11},{"year":2013,"count":17},{"year":2014,"count":30},{"year":2015,"count":33},{"year":2016,"count":31},{"year":2017,"count":33},{"year":2018,"count":30},{"year":2019,"count":41},{"year":2020,"count":43},{"year":2021,"count":49},{"year":2022,"count":43},{"year":2023,"count":40},{"year":2024,"count":47},{"year":2025,"count":32},{"year":2026,"count":18}],"oa_status":"bronze","license":"Springer Nature TDM","oa_locations":[{"url":"https://www.nature.com/articles/ncomms1735.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/ncomms1735.pdf","host_type":"BRONZE"},{"url":"https://www.nature.com/articles/ncomms1735.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/ncomms1735","host_type":"publisher"},{"url":"https://doi.org/10.1038/ncomms1735","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22415822","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3347486","host_type":"repository"},{"url":"https://dx.doi.org/10.1038/ncomms1735","host_type":""}],"fields_of_study":["Calcium signaling and nucleotide metabolism","Plant Molecular Biology Research","Biology","Medicine","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","COS Cells","Calcium","Chlorocebus aethiops","Cholesterol","Cricetinae","Humans","Lysosomes","Macrophages","Mice","Mice, Inbred BALB C","Mice, Knockout","Niemann-Pick Diseases","Patch-Clamp Techniques","Phthalimides","Protein Transport","Quinolines","Sphingomyelin Phosphodiesterase","Sphingomyelins","TRPC Cation Channels","Transient Receptor Potential Channels"],"mesh_terms":["Animals","Calcium","Chlorocebus aethiops","Cholesterol","Cricetinae","Humans","Lysosomes","Macrophages","Mice, Inbred BALB C","Niemann-Pick Diseases","Phthalimides","Quinolines","Sphingomyelin Phosphodiesterase","Sphingomyelins","Mice, Knockout","Patch-Clamp Techniques","COS Cells","Protein Transport","Transient Receptor Potential Channels","TRPC Cation Channels","Mice"],"keywords":["Lysosome","Lysosomal storage disease","Cell biology","Sphingomyelin","Transient receptor potential channel","Chemistry","Mannose 6-phosphate receptor","Niemann–Pick disease","Biochemistry","Calcium","Biology","Cholesterol","Enzyme","Receptor","Mice, Knockout","Niemann-Pick Diseases","Mice, Inbred BALB C","Patch-Clamp Techniques","Macrophages","Phthalimides","Sphingomyelins","Mice","Protein Transport","Sphingomyelin Phosphodiesterase","Cricetinae","COS Cells","Chlorocebus aethiops","Quinolines","Animals","Humans","Lysosomes","TRPC Cation Channels"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"igsr"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-20T00:00:43.747614Z","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":[]}