ArticleThe Journal of biological chemistry2011
Identification of novel anionic phospholipid binding domains in neutral sphingomyelinase 2 with selective binding preference.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Small extracellular vesicles: connecting early life exposure outcomes to air pollution during pregnancy to early childhood health.Environmental health : a global access science source · 2025Pooled it
- Exosome-Mediated Systemic Signaling: Mechanisms, Disease Integration, and Translational Potential.Current issues in molecular biology · 2026Review
- Development of a FRET-Based Assay for Human Neutral Sphingomyelinase 2.Biochemistry · 2026Article
- An update on schistosomicide and tumoricide in the future: arachidonic acid.Lipids in health and disease · 2025Review
- Redefining the Limits of Nanodevices-Based Drug Delivery Systems: Extracellular Vesicles.Pharmaceutics · 2025Review
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Dynamic changes in the proximitome of neutral sphingomyelinase-2 (nSMase2) in TNFα stimulated Jurkat cells.Frontiers in immunology · 2024Article
- The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis.Frontiers in immunology · 2024Review
- Inhibition of neutral sphingomyelinase 2 impairs HIV-1 envelope formation and substantially delays or eliminates viral rebound.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification.International journal of molecular sciences · 2022Review
- A Comprehensive Review on the Interplay betweenCells · 2021Review
- The role of lipids in exosome biology and intercellular communication: Function, analytics and applications.Traffic (Copenhagen, Denmark) · 2021Review
- Exosomal miRNAs: novel players in viral infection.Epigenomics · 2020Review
- The juxtamembrane linker in neutral sphingomyelinase-2 functions as an intramolecular allosteric switch that activates the enzyme.The Journal of biological chemistry · 2019Article
- Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles.Journal of lipid research · 2018Review
- Exosomes-the enigmatic regulators of bone homeostasis.Bone research · 2018Review
- Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease.The EMBO journal · 2017Article
- Structure of human nSMase2 reveals an interdomain allosteric activation mechanism for ceramide generation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.Cell death & disease · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Sphingolipids such as ceramide are recognized as vital regulators of many biological processes. Neutral sphingomyelinase 2 (nSMase2) is one of the key enzymes regulating ceramide production. It was previously shown that the enzymatic activity of nSMase2 was dependent on anionic phospholipids (APLs). In this study, the structural requirements for APL-selective binding of nSMase2 were determined and characterized. Using lipid-protein overlay assays, nSMase2 interacted specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Lipid-protein binding studies of deletion mutants identified two discrete APL binding domains in the N terminus of nSMase2. Further, mutagenesis experiments pinpointed the core sequences and major cationic amino acids in the domains that are necessary for the cooperative activation of nSMase2 by APLs. The first domain included the first amino-terminal hydrophobic segment and Arg-33, which were essential for nSMase2 to interact with APLs. The second binding domain was comprised of the second hydrophobic segment and Arg-92 and Arg-93. Moreover, mutation of one or both domains decreased APL binding and APL-dependent catalytic activity of nSMase2. Further, mutation of both domains in nSMase2 reduced its plasma membrane localization. Finally, these binding domains are also important for the capability of nSMase2 to rescue the defects of yeast lacking the nSMase homologue, ISC1. In conclusion, these data have identified the APL binding domains of nSMase2 for the first time. The analysis of interactions between nSMase2 and APLs will contribute to our understanding of signaling pathways mediated by sphingolipid metabolites.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.