TY - JOUR
T1 - Dynamin is primed at endocytic sites for ultrafast endocytosis
AU - Imoto, Yuuta
AU - Raychaudhuri, Sumana
AU - Ma, Ye
AU - Fenske, Pascal
AU - Sandoval, Eduardo
AU - Itoh, Kie
AU - Blumrich, Eva Maria
AU - Matsubayashi, Hideaki T.
AU - Mamer, Lauren
AU - Zarebidaki, Fereshteh
AU - Söhl-Kielczynski, Berit
AU - Trimbuch, Thorsten
AU - Nayak, Shraddha
AU - Iwasa, Janet H.
AU - Liu, Jian
AU - Wu, Bin
AU - Ha, Taekjip
AU - Inoue, Takanari
AU - Jorgensen, Erik M.
AU - Cousin, Michael A.
AU - Rosenmund, Christian
AU - Watanabe, Shigeki
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/9/7
Y1 - 2022/9/7
N2 - 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.
AB - 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.
KW - Dyn1xA
KW - Dynamin
KW - Dynamin splice variants
KW - Syndapin
KW - endocytosis
KW - flash-and-freeze
KW - liquid condensates
KW - phase separation
KW - synaptic vesicle recycling
KW - ultrafast endocytosis
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U2 - 10.1016/j.neuron.2022.06.010
DO - 10.1016/j.neuron.2022.06.010
M3 - Article
C2 - 35809574
AN - SCOPUS:85135296462
SN - 0896-6273
VL - 110
SP - 2815-2835.e13
JO - Neuron
JF - Neuron
IS - 17
ER -