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Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses

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Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses. / Patzke, Christopher; Brockmann, Marisa M; Dai, Jinye; Gan, Kathlyn J; Grauel, M Katharina; Fenske, Pascal; Liu, Yu; Acuna, Claudio; Rosenmund, Christian; Südhof, Thomas C.

In: CELL, Vol. 179, No. 2, 03.10.2019, p. 498-513.e22.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Patzke, C, Brockmann, MM, Dai, J, Gan, KJ, Grauel, MK, Fenske, P, Liu, Y, Acuna, C, Rosenmund, C & Südhof, TC 2019, 'Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses', CELL, vol. 179, no. 2, pp. 498-513.e22. https://doi.org/10.1016/j.cell.2019.09.011

APA

Patzke, C., Brockmann, M. M., Dai, J., Gan, K. J., Grauel, M. K., Fenske, P., Liu, Y., Acuna, C., Rosenmund, C., & Südhof, T. C. (2019). Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses. CELL, 179(2), 498-513.e22. https://doi.org/10.1016/j.cell.2019.09.011

Vancouver

Patzke C, Brockmann MM, Dai J, Gan KJ, Grauel MK, Fenske P et al. Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses. CELL. 2019 Oct 3;179(2):498-513.e22. https://doi.org/10.1016/j.cell.2019.09.011

Bibtex

@article{d1badaaa272e421dac1a2a86014a61fe,
title = "Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses",
abstract = "Neuromodulators bind to pre- and postsynaptic G protein-coupled receptors (GPCRs), are able to quickly change intracellular cyclic AMP (cAMP) and Ca2+ levels, and are thought to play important roles in neuropsychiatric and neurodegenerative diseases. Here, we discovered in human neurons an unanticipated presynaptic mechanism that acutely changes synaptic ultrastructure and regulates synaptic communication. Activation of neuromodulator receptors bidirectionally controlled synaptic vesicle numbers within nerve terminals. This control correlated with changes in the levels of cAMP-dependent protein kinase A-mediated phosphorylation of synapsin-1. Using a conditional deletion approach, we reveal that the neuromodulator-induced control of synaptic vesicle numbers was largely dependent on synapsin-1. We propose a mechanism whereby non-phosphorylated synapsin-1 {"}latches{"} synaptic vesicles to presynaptic clusters at the active zone. cAMP-dependent phosphorylation of synapsin-1 then removes the vesicles. cAMP-independent dephosphorylation of synapsin-1 in turn recruits vesicles. Synapsin-1 thereby bidirectionally regulates synaptic vesicle numbers and modifies presynaptic neurotransmitter release as an effector of neuromodulator signaling in human neurons.",
keywords = "Animals, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases/metabolism, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Neurotransmitter Agents/metabolism, Presynaptic Terminals/metabolism, Receptors, Neurotransmitter/metabolism, Signal Transduction, Synapsins/metabolism, Synaptic Transmission, Synaptic Vesicles/metabolism",
author = "Christopher Patzke and Brockmann, {Marisa M} and Jinye Dai and Gan, {Kathlyn J} and Grauel, {M Katharina} and Pascal Fenske and Yu Liu and Claudio Acuna and Christian Rosenmund and S{\"u}dhof, {Thomas C}",
note = "Copyright {\textcopyright} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = oct,
day = "3",
doi = "10.1016/j.cell.2019.09.011",
language = "English",
volume = "179",
pages = "498--513.e22",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses

AU - Patzke, Christopher

AU - Brockmann, Marisa M

AU - Dai, Jinye

AU - Gan, Kathlyn J

AU - Grauel, M Katharina

AU - Fenske, Pascal

AU - Liu, Yu

AU - Acuna, Claudio

AU - Rosenmund, Christian

AU - Südhof, Thomas C

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/10/3

Y1 - 2019/10/3

N2 - Neuromodulators bind to pre- and postsynaptic G protein-coupled receptors (GPCRs), are able to quickly change intracellular cyclic AMP (cAMP) and Ca2+ levels, and are thought to play important roles in neuropsychiatric and neurodegenerative diseases. Here, we discovered in human neurons an unanticipated presynaptic mechanism that acutely changes synaptic ultrastructure and regulates synaptic communication. Activation of neuromodulator receptors bidirectionally controlled synaptic vesicle numbers within nerve terminals. This control correlated with changes in the levels of cAMP-dependent protein kinase A-mediated phosphorylation of synapsin-1. Using a conditional deletion approach, we reveal that the neuromodulator-induced control of synaptic vesicle numbers was largely dependent on synapsin-1. We propose a mechanism whereby non-phosphorylated synapsin-1 "latches" synaptic vesicles to presynaptic clusters at the active zone. cAMP-dependent phosphorylation of synapsin-1 then removes the vesicles. cAMP-independent dephosphorylation of synapsin-1 in turn recruits vesicles. Synapsin-1 thereby bidirectionally regulates synaptic vesicle numbers and modifies presynaptic neurotransmitter release as an effector of neuromodulator signaling in human neurons.

AB - Neuromodulators bind to pre- and postsynaptic G protein-coupled receptors (GPCRs), are able to quickly change intracellular cyclic AMP (cAMP) and Ca2+ levels, and are thought to play important roles in neuropsychiatric and neurodegenerative diseases. Here, we discovered in human neurons an unanticipated presynaptic mechanism that acutely changes synaptic ultrastructure and regulates synaptic communication. Activation of neuromodulator receptors bidirectionally controlled synaptic vesicle numbers within nerve terminals. This control correlated with changes in the levels of cAMP-dependent protein kinase A-mediated phosphorylation of synapsin-1. Using a conditional deletion approach, we reveal that the neuromodulator-induced control of synaptic vesicle numbers was largely dependent on synapsin-1. We propose a mechanism whereby non-phosphorylated synapsin-1 "latches" synaptic vesicles to presynaptic clusters at the active zone. cAMP-dependent phosphorylation of synapsin-1 then removes the vesicles. cAMP-independent dephosphorylation of synapsin-1 in turn recruits vesicles. Synapsin-1 thereby bidirectionally regulates synaptic vesicle numbers and modifies presynaptic neurotransmitter release as an effector of neuromodulator signaling in human neurons.

KW - Animals

KW - Cells, Cultured

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - HEK293 Cells

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Neurotransmitter Agents/metabolism

KW - Presynaptic Terminals/metabolism

KW - Receptors, Neurotransmitter/metabolism

KW - Signal Transduction

KW - Synapsins/metabolism

KW - Synaptic Transmission

KW - Synaptic Vesicles/metabolism

U2 - 10.1016/j.cell.2019.09.011

DO - 10.1016/j.cell.2019.09.011

M3 - SCORING: Journal article

C2 - 31585084

VL - 179

SP - 498-513.e22

JO - CELL

JF - CELL

SN - 0092-8674

IS - 2

ER -