ArticleProceedings of the National Academy of Sciences of the United States of America2022
Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- HIV-1 envelope glycoprotein modulates CXCR4 clustering and dynamics on the T cell membrane.eLife · 2026Article
- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- The CXCL12-CXCR4 axis in colorectal cancer: immune regulation, metastatic progression, and therapeutic implications.Frontiers in immunology · 2026Review
- Cholesterol oxidase treatment impairs CXCR4-mediated T cell migration.Cell communication and signaling : CCS · 2025Article
- 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
- Article
- Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain.eLife · 2024Article
- The complex nature of CXCR4 mutations in WHIM syndrome.Frontiers in immunology · 2024Review
- Expanding CXCR4 variant landscape in WHIM syndrome: integrating clinical and functional data for variant interpretation.Frontiers in immunology · 2024Review
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- TrackAnalyzer: A Fiji/ImageJ toolbox for a holistic analysis of tracks.Biological imaging · 2023Article
- Sphingomyelin Depletion Inhibits CXCR4 Dynamics and CXCL12-Mediated Directed Cell Migration in Human T Cells.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemokine receptor nanoscale organization at the cell membrane is orchestrated by the actin cytoskeleton and influences cell responses. Using single-particle tracking analysis we show that CXCR4R334X, a truncated mutant chemokine receptor linked to WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), fails to nanoclusterize after CXCL12 stimulation, and alters the lateral mobility and spatial organization of CXCR4 when coexpressed. These findings correlate with multiple phalloidin-positive protrusions in cells expressing CXCR4R334X, and their inability to correctly sense chemokine gradients. The underlying mechanisms involve inappropriate actin cytoskeleton remodeling due to the inadequate β-arrestin1 activation by CXCR4R334X, which disrupts the equilibrium between activated and deactivated cofilin. Overall, we provide insights into the molecular mechanisms governing CXCR4 nanoclustering, signaling and cell function, and highlight the essential scaffold role of β-arrestin1 to support CXCL12-mediated actin reorganization and receptor clustering. These defects associated with CXCR4R334X expression might contribute to the severe immunological symptoms associated with WHIM syndrome.
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