Dynamin is primed at endocytic sites for ultrafast endocytosis

Dynamin mediates fission of vesicles from the plasma membrane during endocytosis. Typically, dynamin is recruited from the cytosol to endocytic sites, requiring seconds to tens of seconds. However, ultrafast endo-cytosis in neurons internalizes vesicles as quickly as 50 ms during synaptic vesicle recycling. Here, we demonstrate that Dynamin 1 is pre-recruited to endocytic sites for ultrafast endocytosis. Specifically, Dyna-min 1xA, a splice variant of Dynamin 1, interacts with Syndapin 1 to form molecular condensates on the plasma membrane. Single-particle tracking of Dynamin 1xA molecules confirms the liquid-like property of condensates in vivo. When Dynamin 1xA is mutated to disrupt its interaction with Syndapin 1, the conden-sates do not form, and consequently, ultrafast endocytosis slows down by 100-fold. Mechanistically, Synda-pin 1 acts as an adaptor by binding the plasma membrane and stores Dynamin 1xA at endocytic sites. This cache bypasses the recruitment step and accelerates endocytosis at synapses.

Automated summary

This study demonstrates that Dynamin 1 is pre-recruited to endocytic sites for ultrafast endocytosis. Syndapin 1 acts as an adaptor by binding the plasma membrane and storing Dynamin 1xA at endocytic sites, bypassing the recruitment step and accelerating endocytosis. These findings reveal the mechanism of endocytosis and provide new insights into cellular processes.