SYNAPTIC VESICLE ENDOCYTOSIS IMPAIRED BY DISRUPTION OF DYNAMIN-SH3 DOMAIN INTERACTIONS

The proline-rich COOH-terminal region of dynamin binds various Src hom ology 3 (SH3) domain-containing proteins, but the physiological role o f these interactions is unknown. In living nerve terminals, the functi on of the interaction with SH3 domains was examined. Amphiphysin conta ins an SH3 domain and is a major dynamin binding partner at the synaps e. Microinjection of amphiphysin's SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in a n activity-dependent distortion of the synaptic architecture and a dep ression of transmitter release. These findings demonstrate that SH3-me diated interactions are required for dynamin function and support an e ssential role of clathrin-mediated endocytosis in synaptic vesicle rec ycling.