Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The membrane proteins Star and Rhomboid-1 have been genetically defined as the primary regulators of EGF receptor activation in Drosophila, but their molecular mechanisms have been elusive. Both Star and Rhomboid-1 have been assumed to work at the cell surface to control ligand activation. Here, we demonstrate that they control receptor signaling by regulating intracellular trafficking and proteolysis of the ligand Spitz. Star is present throughout the secretory pathway and is required to export Spitz from the endoplasmic reticulum to the Golgi apparatus. Rhomboid-1 is localized in the Golgi, where it promotes the cleavage of Spitz. This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface.


Journal article



Publication Date





161 - 171


Animals, Biotinylation, Blotting, Western, COS Cells, Drosophila, Drosophila Proteins, Endoplasmic Reticulum, Epidermal Growth Factor, Glycosylation, Golgi Apparatus, Green Fluorescent Proteins, Immunohistochemistry, Ligands, Luminescent Proteins, Membrane Proteins, Microscopy, Fluorescence, Models, Biological, Phosphoproteins, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Protein Transport, Signal Transduction