Summary of Study ST002150
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001363. The data can be accessed directly via it's Project DOI: 10.21228/M8J708 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002150 |
| Study Title | Sphingomyelin depletion inhibits CXCR4 dynamics and CXCL12-mediated directed cell migration in human T cells |
| Study Summary | 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-molecule dynamic approaches 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 neutral 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 |
| Institute | Universidad CEU San Pablo |
| Last Name | Gonzalez-Riano |
| First Name | Carolina |
| Address | km 0, Universidad CEU-San Pablo Urbanización Montepríncipe. M-501 |
| carolina.gonzalezriano@ceu.es | |
| Phone | 646251045 |
| Submit Date | 2022-04-22 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-05-09 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002229 |
| Collection Summary: | HEK-293T cells were obtained from the ATCC (CRL-11268) and human Jurkat leukemia CD4+ cells were kindly donated by Dr. J. Alcamí (Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain). When needed, Jurkat cells lacking endogenous CXCR4 expression (Jurkat-/-) were transiently transfected with CXCR4-AcGFP (20 µg; JK-/-X4) using a BioRad electroporator (20 × 106 cells/400 µL RPMI 1640 with 10% fetal calf serum) and analyzed 24 hours later. Human peripheral blood mononuclear cells were isolated from buffy coats by centrifugation through FicollPaque PLUS density gradients (GE Healthcare, Wakuesha, WI) at 760 × g for 30 minutes at room temperature (RT). They were then in vitro activated with 20 U/mL of IL-2 (Teceleukin; Roche, Nutley, NJ) and 5 µg/mL phytohemagglutinin PHA (Roche) to generate T cell blasts. |
| Sample Type: | HEK cells |
