Glucosylceramide synthesis is required for basic fibroblast growth factor and laminin to stimulate axonal growth.
To test the hypothesis that neuronal growth requires the synthesis and supply of new membrane components to the growing neurite, we have examined the relationship between the synthesis of sphingolipids and the ability of two growth factors, basic fibroblast growth factor (bFGF) and laminin, to stimulate axonal growth in cultured hippocampal neurons. Both bFGF and laminin stimulate axonal growth by approximately fourfold; but the stimulatory effects of both factors can be abolished completely by two inhibitors of sphingolipid synthesis, fumonisin B1 and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. By using these inhibitors, together with two stereoisomers of short acyl chain derivatives of ceramide, only one of which is metabolized to glucosylceramide, we demonstrate that ongoing synthesis of glucosylceramide, the simplest glycosphingolipid, is a prerequisite for both bFGF and laminin to stimulate axon growth. These data imply that the ability of a growth factor to stimulate neuronal growth is dependent on the synthesis of an essential membrane lipid.
Boldin
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S
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Futerman
A H
AH
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002264:Carboxylic Acids / Q000494:pharmacology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D037341:Fumonisins; D005963:Glucosylceramides / Q000096:biosynthesis*; D006624:Hippocampus / Q000166:cytology; D007797:Laminin / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D011107:Polylysine; D013237:Stereoisomerism; D013723:Teratogens / Q000494:pharmacology
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D002518:Ceramides; D037341:Fumonisins; D005963:Glucosylceramides; D007797:Laminin; D009025:Morpholines; D013723:Teratogens; D016222:Fibroblast Growth Factor 2; D011107:Polylysine; C056933:fumonisin B1; C033110:RV 538; C037974:N-(7-(4-nitrobenzo-2-oxa-1,3-diazole))-6-aminocaproyl sphingosine; D009327:4-Chloro-7-nitrobenzofurazan