Despite being present in all eukaryotic cell membranes and being implicated in a wide range of biological processes, including human disease, little is known about the in vivo function of glycosphingolipids (GSLs). Now, on , Sandrine Pizette and co-workers reveal that GSLs are required for the full activation of EGFR signalling during Drosophila oogenesis, and that they regulate the formation of an extracellular gradient of the EGFR ligand Gurken. Egghead (Egh) and Brainiac (Brn) are two non-redundant Drosophilaglycosyltransferases that are crucial for GSL biosynthesis. Using eghand brn mutant flies, the researchers show that during oogenesis GSLs are required in oocytes, which produce Gurken, but not in follicle cells,which express EGFR. Furthermore, they demonstrate that GSLs do not regulate Gurken trafficking or secretion, as previous data have suggested. Instead,GSLs shape an extracellular Gurken gradient by allowing Gurken to diffuse efficiently. Future work and novel tools will be required, however, to fully understand the mechanism by which GSLs affect Gurken diffusion.
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