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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Limatola C,Massa V,Lauro C,Catalano M,Giovanetti A,Nuccitelli S,Spinedi A

doi

10.1016/j.febslet.2007.05.003

subject

Has Abstract

pub_date

2007-06-12 00:00:00

pages

2641-6

issue

14

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(07)00531-5

journal_volume

581

pub_type

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