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 endocytosis 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, Dynamin 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 condensates do not form, and consequently, ultrafast endocytosis slows down by 100-fold. Mechanistically, Syndapin 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. [Display omitted] • A splice variant of Dynamin 1, Dyn1xA, specifically mediates ultrafast endocytosis • Dyn1xA forms condensates with Syndapin 1 and pre-accumulates at endocytic zones • Syndapin 1 acts as a hub between Dyn1xA and the plasma membrane • Disruption of Dyn1xA condensates slows down the kinetics of endocytosis by 100-fold Imoto et al. demonstrate that a splice variant of Dynamin 1, Dyn1xA, mediates vesicle scission during ultrafast endocytosis. For such a rapid event, Dyn1xA molecules are concentrated at endocytic zones through molecular condensation with Syndapin 1. This cache of Dyn1xA accelerates the kinetics of endocytosis by 100-fold. [ABSTRACT FROM AUTHOR]