A single PXXP motif in the C-terminal region of srGAP3 mediates binding to multiple SH3 domains

The Slit-Robo GTPase-activating protein 3 (srGAP3) has been implicated in different critical aspects of neuronal development. These findings have mainly been based on the characterisation of the three conserved globular N-terminal domains, while the function of the C-terminal region (CTR) is still unknown. We show that this predicted unstructured region acts as an adaptor by binding to the endocytic proteins Amphiphysin, Endophilin-A2, Endophilin-A1, as well as the Ras signalling protein Grb2. All these interactions depend on a single proline-rich motif in the CTR and the Src-homology 3 domains of the binding partners. Via these interactions srGAP3 could link receptor signalling events to the endocytic machinery. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.