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 Lettjournal_title
FEBS lettersauthors
Limatola C,Massa V,Lauro C,Catalano M,Giovanetti A,Nuccitelli S,Spinedi Adoi
10.1016/j.febslet.2007.05.003subject
Has Abstractpub_date
2007-06-12 00:00:00pages
2641-6issue
14eissn
0014-5793issn
1873-3468pii
S0014-5793(07)00531-5journal_volume
581pub_type
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