ArticleCell2018
Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 2 of them syntheses that pooled it.
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170citing papers in PubMed, 2 pooled it
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170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 281 citations in OpenAlex.
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- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- A CRISPR activation screen identifies CH25H as a restriction factor against influenza viruses by targeting accessible cholesterol.Emerging microbes & infections · 2026Article
- The orientation of cholesterol's hydroxy group affects its membrane dynamics and intracellular transport.iScience · 2026Article
- Does Complexation of Plasma Membrane Cholesterol with Phospholipids Determine its Transbilayer Distribution?The Journal of membrane biology · 2026Article
- Design and structural basis of selective nonsteroidal inhibitors of aster cholesterol trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Nature communications · 2026Article
- Photosensitizer proximity labeling captures the lipid and protein interactomes.Nature chemical biology · 2026Article
- Chromatin accessibility of the jejunum in two high-yielding laying hen strains under divergent mineral phosphorus supply during the transition to egg laying.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
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- Singlet oxygen spills sterol secrets.Nature chemical biology · 2026Article
- The membrane transition strongly enhances biopolymer condensation through prewetting.Nature chemical biology · 2026Article
- Microsomal triglyceride transfer protein restricts steroid production in Leydig cells by regulating SREBP2.iScience · 2026Article
- HKDC1 contributes to aberrant lysosome-mitochondria contact in Niemann-Pick disease type C.bioRxiv : the preprint server for biology · 2026Article
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- MCTP1 and MCTP2 promote ER-PM contact sites and regulate PI4P homeostasis and cell migration.Molecular biology of the cell · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- The non-vesicular cholesterol transporter GRAMD1C is a pan-coronavirus antiviral target.PLoS biology · 2026Article
- A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites.Nature communications · 2026Article
110 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 8 institutions in 4 countries.
Jaspreet SandhuDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Shiqian LiDepartment of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland; Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
Louise FairallInstitute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK.
Simon G PfistererDepartment of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland; Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
Jennifer E GurnettInstitute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK.
Xu XiaoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Thomas A WestonDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dipti VashiInstitute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK.
Alessandra FerrariDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jose L OrozcoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Celine L HartmanEdward A. Doisy Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
David StrugatskyDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stephen D LeeDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cuiwen HeDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cynthia HongDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Haibo JiangCentre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth 6009, Australia.
Laurent A BentolilaCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095, USA.
Alberto T GattaDepartment of Cell Biology, UCL Institute of Ophthalmology, London, UK.
Tim P LevineDepartment of Cell Biology, UCL Institute of Ophthalmology, London, UK.
Annie FerngIonis Pharmaceuticals, Carlsbad, CA 92008, USA.
Richard LeeIonis Pharmaceuticals, Carlsbad, CA 92008, USA.
David A FordEdward A. Doisy Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Stephen G YoungDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elina IkonenDepartment of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland; Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
John W R SchwabeInstitute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ptontonoz@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Leicester · GBIonis Pharmaceuticals (United States) · USSaint Louis University · USUniversity College London · GBUniversity of Helsinki · FIMinerva Foundation · FIThe University of Western Australia · AU
Funding
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9MUnderstanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2019 to 2023
$11.7MMARC U*STAR Program at the University of California, Los AngelesT34GM008563 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCEVOY, MEGAN M, POE, GINA R · 1996 to 2023
$9.7MVascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4MNUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESISR01HL066088 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2001 to 2018
$5.4MChlorinated lipids in sepsisR01GM115553 · NIGMS · SAINT LOUIS UNIVERSITY · PI FORD, DAVID A., MCHOWAT, JANE · 2015 to 2021
$3.0MDesigned Small Molecule Inhibitors of Ghrelin O-Acyl TransferaseR01DK100627 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HARRAN, PATRICK G., TONTONOZ, PETER J · 2014 to 2018
$2.8MLipid-Responsive E3 ubiquitin ligases in cholesterol metabolism and atheroscierosisR01HL136618 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2018 to 2021
$2.4MTSQ QUANTUM ESI-MS SURVEYOR BUNDLE: RENAL, HEART, RETINAL, &LUNG DISEASESS10RR019232 · NCRR · SAINT LOUIS UNIVERSITY · PI FORD, DAVID A. · 2004 to 2004
$339kBiotechnology and Biological Sciences Research Council BB/M011801/1Biotechnology and Biological Sciences Research Council BB/P003818/1NCRR NIH HHS S10 RR019232NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL066088NHLBI NIH HHS R01 HL136618NHLBI NIH HHS T32 HL069766NIDDK NIH HHS R01 DK100627NIGMS NIH HHS R01 GM115553NIGMS NIH HHS T32 GM008042NIGMS NIH HHS T34 GM008563Wellcome TrustWellcome Trust WT100237
Abstract
The mechanisms underlying sterol transport in mammalian cells are poorly understood. In particular, how cholesterol internalized from HDL is made available to the cell for storage or modification is unknown. Here, we describe three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate its removal from the plasma membrane. The crystal structure of the central domain of Aster-A broadly resembles the sterol-binding fold of mammalian StARD proteins, but sequence differences in the Aster pocket result in a distinct mode of ligand binding. The Aster N-terminal GRAM domain binds phosphatidylserine and mediates Aster recruitment to plasma membrane-ER contact sites in response to cholesterol accumulation in the plasma membrane. Mice lacking Aster-B are deficient in adrenal cholesterol ester storage and steroidogenesis because of an inability to transport cholesterol from SR-BI to the ER. These findings identify a nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals.
Indexed as
3T3 CellsAnimalsBiological TransportCarrier ProteinsCD36 AntigensCell LineCell MembraneCHO CellsCholesterolCholesterol, HDLCricetulusEndoplasmic ReticulumHumansMembrane ProteinsMiceMice, Inbred C57BLCarrier ProteinsCD36 AntigensCholesterolCholesterol, HDLGRAMD1A protein, humanMembrane ProteinsSterolscholesterolHDL metabolismLXRmembrane contact sitesnonvesicular transportSR-BISREBPsteroidogenesis
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