Dynamin is primed at endocytic sites for ultrafast endocytosis

Yuuta Imoto; Sumana Raychaudhuri; Ye Ma; Pascal Fenske; Eduardo Sandoval; Kie Itoh; Eva Maria Blumrich; Hideaki T. Matsubayashi; Lauren Mamer; Fereshteh Zarebidaki; Berit Söhl-Kielczynski; Thorsten Trimbuch; Shraddha Nayak; Janet H. Iwasa; Jian Liu; Bin Wu; Taekjip Ha; Takanari Inoue; Erik M. Jorgensen; Michael A. Cousin; Christian Rosenmund; Shigeki Watanabe

doi:10.1016/j.neuron.2022.06.010

Dynamin is primed at endocytic sites for ultrafast endocytosis

Yuuta Imoto, Sumana Raychaudhuri, Ye Ma, Pascal Fenske, Eduardo Sandoval, Kie Itoh, Eva Maria Blumrich, Hideaki T. Matsubayashi, Lauren Mamer, Fereshteh Zarebidaki, Berit Söhl-Kielczynski, Thorsten Trimbuch, Shraddha Nayak, Janet H. Iwasa, Jian Liu, Bin Wu, Taekjip Ha, Takanari Inoue, Erik M. Jorgensen, Michael A. CousinChristian Rosenmund, Shigeki Watanabe

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	2815-2835.e13
Journal	Neuron
Volume	110
Issue number	17
DOIs	https://doi.org/10.1016/j.neuron.2022.06.010
State	Published - Sep 7 2022

Keywords

Dyn1xA
Dynamin
Dynamin splice variants
Syndapin
endocytosis
flash-and-freeze
liquid condensates
phase separation
synaptic vesicle recycling
ultrafast endocytosis

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2022.06.010

Cite this

Imoto, Y., Raychaudhuri, S., Ma, Y., Fenske, P., Sandoval, E., Itoh, K., Blumrich, E. M., Matsubayashi, H. T., Mamer, L., Zarebidaki, F., Söhl-Kielczynski, B., Trimbuch, T., Nayak, S., Iwasa, J. H., Liu, J., Wu, B., Ha, T., Inoue, T., Jorgensen, E. M., ... Watanabe, S. (2022). Dynamin is primed at endocytic sites for ultrafast endocytosis. Neuron, 110(17), 2815-2835.e13. https://doi.org/10.1016/j.neuron.2022.06.010

Imoto, Y, Raychaudhuri, S, Ma, Y, Fenske, P, Sandoval, E, Itoh, K, Blumrich, EM, Matsubayashi, HT, Mamer, L, Zarebidaki, F, Söhl-Kielczynski, B, Trimbuch, T, Nayak, S, Iwasa, JH, Liu, J , Wu, B, Ha, T, Inoue, T, Jorgensen, EM, Cousin, MA, Rosenmund, C & Watanabe, S 2022, 'Dynamin is primed at endocytic sites for ultrafast endocytosis', Neuron, vol. 110, no. 17, pp. 2815-2835.e13. https://doi.org/10.1016/j.neuron.2022.06.010

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title = "Dynamin is primed at endocytic sites for ultrafast endocytosis",

abstract = "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.",

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doi = "10.1016/j.neuron.2022.06.010",

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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

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.

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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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SN - 0896-6273

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SP - 2815-2835.e13

JO - Neuron

JF - Neuron

IS - 17

ER -

Dynamin is primed at endocytic sites for ultrafast endocytosis

Abstract

Keywords

ASJC Scopus subject areas

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