Evidence for a role of glycosphingolipids in CXCR4-dependent cell migration.

Abstract

Chemotaxis induction is a major effect evoked by stimulation of the chemokine receptor CXCR4 with its sole ligand CXCL12. We now report that treatment of CHP-100 human neuroepithelioma cells with the glucosylceramide synthase (GCS) inhibitor DL-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol inhibits CXCR4-dependent chemotaxis. We provide evidence that the phenomenon is not due to unspecific effects of the inhibitor employed and that inhibition of GCS neither affects total or plasmamembrane CXCR4 expression, nor CXCL12-induced Ca(2+) mobilization. The effects of the GCS inhibitor on impairment of CXCL12-induced cell migration temporally correlated with a pronounced downregulation of neutral glycosphingolipids, particularly glucosylceramide, and with a delayed and more moderate downregulation of gangliosides; moreover, exogenously administered glycosphingolipids allowed resumption of CXCR4-dependent chemotaxis. Altogether our results provide evidence, for the first time, for a role glycosphingolipids in sustaining CXCL12-induced cell migration.

• Authors: Cristina Limatola, Valeria Massa, Clotilde Lauro, Myriam Catalano, Anna Giovanetti, Silvia Nuccitelli, Angelo Spinedi
• Journal: FEBS letters (FEBS Lett) Vol. 581 Issue 14 Pg. 2641-6 (Jun 12 2007) ISSN: 0014-5793 [Print] England
• PMID: 17511990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol
• CXCL12 protein, human
• Chemokine CXCL12
• Chemokines, CXC
• Enzyme Inhibitors
• Glycosphingolipids
• Propanolamines
• Pyrrolidines
• Receptors, CXCR4
• Glucosyltransferases
• ceramide glucosyltransferase

Topics

• Blotting, Western
• Cell Line, Tumor
• Cell Movement (drug effects, physiology)
• Chemokine CXCL12
• Chemokines, CXC (metabolism, pharmacology)
• Chemotaxis (drug effects)
• Enzyme Inhibitors (pharmacology)
• Flow Cytometry
• Glucosyltransferases (antagonists & inhibitors, metabolism)
• Glycosphingolipids (metabolism, physiology)
• Humans
• Propanolamines (pharmacology)
• Pyrrolidines (pharmacology)
• Receptors, CXCR4 (metabolism, physiology)
• Time Factors