ArticleFrontiers in immunology2022
Sphingomyelin Depletion Inhibits CXCR4 Dynamics and CXCL12-Mediated Directed Cell Migration in Human T Cells.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- HIV-1 envelope glycoprotein modulates CXCR4 clustering and dynamics on the T cell membrane.eLife · 2026Article
- TRAM-LAG1-CLN8 domain-containing protein TMEM56 regulates cell migration by changing intracellular ceramide levels.BMC biology · 2026Article
- Cholesterol oxidase treatment impairs CXCR4-mediated T cell migration.Cell communication and signaling : CCS · 2025Article
- Exploring the effect of canine cancer-associated fibroblasts on T cell dynamics through the CXCL12/CXCR4 axis modulated by TGF-β1.Scientific reports · 2025Article
- CXCL12-targeting siRNA nanoparticles alleviate immunosuppression and inhibit tumor progression in esophageal squamous cell carcinoma.Journal of nanobiotechnology · 2025Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lower Sphingomyelin SM 42:1 Plasma Level in Coronary Artery Disease-Preliminary Study.International journal of molecular sciences · 2025Article
- Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain.eLife · 2024Article
- Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing.Journal of neuroinflammation · 2024Article
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- Chemokine Receptor Antagonists Prevent and Reverse Cofilin-Actin Rod Pathology and Protect Synapses in Cultured Rodent and Human iPSC-Derived Neurons.Biomedicines · 2024Article
- The complex nature of CXCR4 mutations in WHIM syndrome.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingolipids, ceramides and cholesterol are integral components of cellular membranes, and they also play important roles in signal transduction by regulating the dynamics of membrane receptors through their effects on membrane fluidity. Here, we combined biochemical and functional assays with single-particle tracking analysis of diffusion in the plasma membrane to demonstrate that the local lipid environment regulates CXCR4 organization and function and modulates chemokine-triggered directed cell migration. Prolonged treatment of T cells with bacterial sphingomyelinase promoted the complete and sustained breakdown of sphingomyelins and the accumulation of the corresponding ceramides, which altered both membrane fluidity and CXCR4 nanoclustering and dynamics. Under these conditions CXCR4 retained some CXCL12-mediated signaling activity but failed to promote efficient directed cell migration. Our data underscore a critical role for the local lipid composition at the cell membrane in regulating the lateral mobility of chemokine receptors, and their ability to dynamically increase receptor density at the leading edge to promote efficient cell migration.
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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 Socratic graph.