Synaptic Vesicle Recycling Through the Lens of Ultrafast Endocytosis

The mechanisms underlying synaptic vesicle endocytosis remain controversial. In the 1970s, Heuser and Reese put forward a hypothesis that clathrin-mediated endocytosis is the predominant vesicle retrieval mechanism. In their seminal papers, another pathway was also described: uncoated large vesicles or cisternae emanating from the plasma membrane 1 s after a single stimulus. This pathway likely represents a recently described ultrafast endocytic pathway that recovers synaptic vesicles during physiological stimuli. Had we known of the existence of ultrafast endocytosis or paid more attention to the cisternae-based uptake pathway, would the experimental results over subsequent years have been interpreted differently? Here, I retrospectively review the literature on synaptic vesicle recycling through the lens of ultrafast endocytosis.