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

Cristina Limatola, Valeria Massa, Clotilde Lauro, Myriam Catalano, Anna Giovanetti, Silvia Nuccitelli, Angelo Spinedi

Research output: Contribution to journalArticle

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)2641-2646
Number of pages6
JournalFEBS Letters
Volume581
Issue number14
DOIs
Publication statusPublished - Jun 12 2007

Keywords

  • Chemotaxis
  • CXCR4
  • Glycosphingolipids
  • Neuroepithelioma

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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