Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling

Nucleoside diphosphate kinase (NDK), an enzyme encoded by the Drosophila ab normal wing discs (awd) or human nm23 tumor suppressor genes, generates nuc leoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of the dynamin GTPase is required, awd mutations lower the temperature at whic h behavioral paralysis, synaptic failure, and blocked membrane internalizat ion occur at dynamin-deficient, shi(ts), mutant nerve terminals. Hypomorphi c awd alleles display shi(ts)-like defects. NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. We sug gest a model in which dynamin activity in nerve terminals is highly depende nt on NDK-mediated supply of GTP. This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis , probably of activated growth factor receptors, is an important tumor supp ressor activity in vivo.