{"doi":"10.3390/biom10060928","title":"ORP5 and ORP8: Sterol Sensors and Phospholipid Transfer Proteins at Membrane Contact Sites?","abstract":"<jats:p>Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.</jats:p>","journal":"Biomolecules","year":2020,"id":18529,"datarank":1.0182439443229594,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.49376781010298737,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.49376781010298737,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":29,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":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":128461,"name":"Vladimir Girik","orcid":null,"position":1,"is_corresponding":false},{"id":128462,"name":"Paula Nunes-Hasler","orcid":"0000-0002-4598-685X","position":2,"is_corresponding":false},{"id":128460,"name":"Nina Criado Santos","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32570981","pmcid":"PMC7356933","openalex_id":"https://openalex.org/W3036788952","authors":[],"funders":[{"funder_name":"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung","grant_id":"310030_189094","title":null},{"funder_name":"Stiftung Professor Dr. Max Cloëtta","grant_id":"2019 Medical Researcher Award","title":null},{"funder_name":"Novartis Stiftung für Medizinisch-Biologische Forschung","grant_id":"17B078","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"189094","title":"Exploring the ER-phagosome connection during antigen cross-presentation"},{"funder_name":"Swiss National Science Foundation","grant_id":"310030","title":null}],"total_grants":5,"fwci":3.5056,"citation_percentile":0.93373413,"influential_citations":0,"citation_trend":[{"year":2021,"count":4},{"year":2022,"count":8},{"year":2023,"count":5},{"year":2024,"count":7},{"year":2025,"count":4},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2218-273X/10/6/928/pdf","host_type":"journal"},{"url":"https://www.mdpi.com/2218-273X/10/6/928/pdf","host_type":"GOLD"},{"url":"https://www.mdpi.com/2218-273X/10/6/928/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/biom10060928","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32570981","host_type":"repository"},{"url":"https://archive-ouverte.unige.ch/unige:139346","host_type":"repository"},{"url":"https://doaj.org/article/0277892c25fd4ec98ecf41f526278290","host_type":"repository"},{"url":"http://doi.org/10.3390/biom10060928","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7356933","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7356933","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7356933?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/biom10060928","host_type":""},{"url":"https://dx.doi.org/10.3390/biom10060928","host_type":""},{"url":"https://sonar.ch/global/documents/171468","host_type":""}],"fields_of_study":["Cholesterol and Lipid Metabolism","Lipid Membrane Structure and Behavior","Cellular transport and secretion","Chemistry","Medicine","Biology","0301 basic medicine","ddc:616.07","03 medical and health sciences","0303 health sciences","Animals","Cell Membrane","Endoplasmic Reticulum","Humans","Phospholipid Transfer Proteins","Receptors, Steroid","Sterols","Oxysterol Binding Proteins"],"mesh_terms":["Oxysterol Binding Proteins","Animals","Cell Membrane","Endoplasmic Reticulum","Humans","Receptors, Steroid","Sterols","Phospholipid Transfer Proteins"],"keywords":["Plant lipid transfer proteins","Membrane contact site","Endoplasmic reticulum","Phosphatidylinositol","Phospholipid transfer protein","Cell biology","Phospholipid","Oxysterol","Sterol","Phospholipid scramblase","Phosphatidylserine","Biology","Transmembrane protein","Lipid droplet","Biochemistry","Membrane protein","Chemistry","Cholesterol","Integral membrane protein","Receptor","Signal transduction","Membrane","Ptdins(4,5)p2","Ptdins","Ptdins4p","Osbpl5","Osbpl8","Cortical Endoplasmic Reticulum","Oxysterol Binding Protein Like 5 And 8","Receptors, Steroid","Oxysterol Binding Proteins","Review","616.07","Microbiology","Animals","Humans","Phospholipid Transfer Proteins","Cell Membrane","QR1-502","Sterols"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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