ArticleiScience2019
A CRISPR Screen Identifies LAPTM4A and TM9SF Proteins as Glycolipid-Regulating Factors.
Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- CRISPR-Cas9 screening revealsMolecular therapy. Advances · 2026Article
- Glycosphingolipids are essential entry factors for non-influenza orthomyxoviruses.The Journal of general virology · 2026Article
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- Ceramide disrupts TM9SF2-PGK1 axis to redirect PD-L1 trafficking and enhance antitumor immunity.Nature communications · 2026Article
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- Siamese Twins: The Multimodular Mechanisms of Golgi Maturation and Glycan Synthesis Are Coupled at Their Core.Sub-cellular biochemistry · 2026Review
- Article
- Dysregulation of PI4P in the trans Golgi regions activates the mammalian Golgi stress response.The Journal of biological chemistry · 2025Article
- LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.Journal of cellular and molecular medicine · 2025Article
- CRISPR screens and lectin microarrays identify high mannose N-glycan regulators.Nature communications · 2024Article
- Human Gb3/CD77 synthase: a glycosyltransferase at the crossroads of immunohematology, toxicology, and cancer research.Cellular & molecular biology letters · 2024Review
- Genetics of glycosylation in mammalian development and disease.Nature reviews. Genetics · 2024Review
- ZNF692 promotes the migration and response to immunotherapy of clear cell renal cell carcinoma cells by targeting metabolic pathway.Discover oncology · 2024Article
- Article
- CRISPR screens and lectin microarrays identify novel high mannose N-glycan regulators.bioRxiv : the preprint server for biology · 2024Article
- Exploring common biomarkers of ischemic stroke and obstructive sleep apnea through bioinformatics analysis.PloS one · 2024Article
- Syntaxin-5's flexibility in SNARE pairing supports Golgi functions.Traffic (Copenhagen, Denmark) · 2023Article
- Gaining New Insights into Fundamental Biological Pathways by Bacterial Toxin-Based Genetic Screens.Bioengineering (Basel, Switzerland) · 2023Review
- The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi.The Journal of cell biology · 2023Article
- FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins.Life science alliance · 2023Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosphingolipids (GSLs) are produced by various GSL-synthesizing enzymes, but post-translational regulation of these enzymes is incompletely understood. To address this knowledge disparity, we focused on biosynthesis of globotriaosylceramide (Gb3), the Shiga toxin (STx) receptor, and performed a genome-wide CRISPR/CAS9 knockout screen in HeLa cells using STx1-mediated cytotoxicity. We identified various genes including sphingolipid-related genes and membrane-trafficking genes. In addition, we found two proteins, LAPTM4A and TM9SF2, for which physiological roles remain elusive. Disruption of either LAPTM4A or TM9SF2 genes reduced Gb3 biosynthesis, resulting in accumulation of its precursor, lactosylceramide. Loss of LAPTM4A decreased endogenous Gb3 synthase activity in a post-transcriptional mechanism, whereas loss of TM9SF2 did not affect Gb3 synthase activity but instead disrupted localization of Gb3 synthase. Furthermore, the Gb3-regulating activity of TM9SF2 was conserved in the TM9SF family. These results provide mechanistic insight into the post-translational regulation of the activity and localization of Gb3 synthase.
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