Sphingomyelin Depletion Inhibits CXCR4 Dynamics and CXCL12-Mediated Directed Cell Migration in Human T Cells.

Autor:	Gardeta SR; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., García-Cuesta EM; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., D'Agostino G; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., Soler Palacios B; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., Quijada-Freire A; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., Lucas P; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., Bernardino de la Serna J; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Central Laser Facility, Rutherford Appleton Laboratory, Medical Research Council-Research Complex at Harwell, Science and Technology Facilities Council, Harwell, United Kingdom.; National Institute for Health and Care Research Imperial Biomedical Research Center, London, United Kingdom., Gonzalez-Riano C; Metabolomic and Bioanalysis Center (CEMBIO), Pharmacy Faculty, Centro de Estudios Universitarios Universities, Madrid, Spain., Barbas C; Metabolomic and Bioanalysis Center (CEMBIO), Pharmacy Faculty, Centro de Estudios Universitarios Universities, Madrid, Spain., Rodríguez-Frade JM; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain., Mellado M; Chemokine Signaling Group, Department of Immunology and Oncology, National Center for Biotechnology/Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jul 12; Vol. 13, pp. 925559. Date of Electronic Publication: 2022 Jul 12 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.925559
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Gardeta, García-Cuesta, D’Agostino, Soler Palacios, Quijada-Freire, Lucas, Bernardino de la Serna, Gonzalez-Riano, Barbas, Rodríguez-Frade and Mellado.)
Databáze:	MEDLINE
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