GTP-independent rapid and slow endocytosis at a central synapse

Vesicle endocytosis is essential for maintaining synaptic transmission. Its key step, membrane scission, is thought to be mediated by the GTPase dynamin in all forms of endocytosis at synapses. Our findings indicate that GTP-independent and probably dynamin-independent endocytosis co-exist with GTP- and dynamin-dependent endocytosis at the same synaptic nerve terminal, the calyx of Held, in rats. This previously undescribed form of endocytosis could be slow (tens of seconds) and/or rapid (a few seconds), similar to GTP- and dynamin-dependent endocytosis. It was activated during intense stimulation, whereas GTP- and dynamin-dependent endocytosis dominated during mild stimulation. These results establish a new model, in which vesicles are divided into two pools depending on their requirement for GTP and dynamin for retrieval. The GTP- and dynamin-dependent pool has higher priority for release and retrieval, but limited capacity, saturation of which leads to release and thus retrieval of GTP- and dynamin-independent vesicles.