Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation

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

Standard

Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation. / Jusyte, Meida; Blaum, Natalie; Böhme, Mathias A.; Berns, Manon M.M.; Bonard, Alix E.; Vámosi, Ábel B.; Pushpalatha, Kavya V.; Kobbersmed, Janus R.L.; Walter, Alexander M.

In: Cell Reports, Vol. 42, No. 6, 112541, 2023.

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

Harvard

Jusyte, M, Blaum, N, Böhme, MA, Berns, MMM, Bonard, AE, Vámosi, ÁB, Pushpalatha, KV, Kobbersmed, JRL & Walter, AM 2023, 'Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation', Cell Reports, vol. 42, no. 6, 112541. https://doi.org/10.1016/j.celrep.2023.112541

APA

Jusyte, M., Blaum, N., Böhme, M. A., Berns, M. M. M., Bonard, A. E., Vámosi, Á. B., Pushpalatha, K. V., Kobbersmed, J. R. L., & Walter, A. M. (2023). Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation. Cell Reports, 42(6), [112541]. https://doi.org/10.1016/j.celrep.2023.112541

Vancouver

Jusyte M, Blaum N, Böhme MA, Berns MMM, Bonard AE, Vámosi ÁB et al. Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation. Cell Reports. 2023;42(6). 112541. https://doi.org/10.1016/j.celrep.2023.112541

Author

Jusyte, Meida ; Blaum, Natalie ; Böhme, Mathias A. ; Berns, Manon M.M. ; Bonard, Alix E. ; Vámosi, Ábel B. ; Pushpalatha, Kavya V. ; Kobbersmed, Janus R.L. ; Walter, Alexander M. / Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation. In: Cell Reports. 2023 ; Vol. 42, No. 6.

Bibtex

@article{04d18469199a4634891e922f8fe7c898,
title = "Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation",
abstract = "Presynaptic plasticity adjusts neurotransmitter (NT) liberation. Short-term facilitation (STF) tunes synapses to millisecond repetitive activation, while presynaptic homeostatic potentiation (PHP) of NT release stabilizes transmission over minutes. Despite different timescales of STF and PHP, our analysis of Drosophila neuromuscular junctions reveals functional overlap and shared molecular dependence on the release-site protein Unc13A. Mutating Unc13A's calmodulin binding domain (CaM-domain) increases baseline transmission while blocking STF and PHP. Mathematical modeling suggests that Ca2+/calmodulin/Unc13A interaction plastically stabilizes vesicle priming at release sites and that CaM-domain mutation causes constitutive stabilization, thereby blocking plasticity. Labeling the functionally essential Unc13A MUN domain reveals higher STED microscopy signals closer to release sites following CaM-domain mutation. Acute phorbol ester treatment similarly enhances NT release and blocks STF/PHP in synapses expressing wild-type Unc13A, while CaM-domain mutation occludes this, indicating common downstream effects. Thus, Unc13A regulatory domains integrate signals across timescales to switch release-site participation for synaptic plasticity.",
keywords = "CP: Neuroscience, neurotransmitter release sites, presynaptic homeostatic potentiation, short-term facilitation, synaptic plasticity, Unc13A",
author = "Meida Jusyte and Natalie Blaum and B{\"o}hme, {Mathias A.} and Berns, {Manon M.M.} and Bonard, {Alix E.} and V{\'a}mosi, {{\'A}bel B.} and Pushpalatha, {Kavya V.} and Kobbersmed, {Janus R.L.} and Walter, {Alexander M.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.celrep.2023.112541",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation

AU - Jusyte, Meida

AU - Blaum, Natalie

AU - Böhme, Mathias A.

AU - Berns, Manon M.M.

AU - Bonard, Alix E.

AU - Vámosi, Ábel B.

AU - Pushpalatha, Kavya V.

AU - Kobbersmed, Janus R.L.

AU - Walter, Alexander M.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Presynaptic plasticity adjusts neurotransmitter (NT) liberation. Short-term facilitation (STF) tunes synapses to millisecond repetitive activation, while presynaptic homeostatic potentiation (PHP) of NT release stabilizes transmission over minutes. Despite different timescales of STF and PHP, our analysis of Drosophila neuromuscular junctions reveals functional overlap and shared molecular dependence on the release-site protein Unc13A. Mutating Unc13A's calmodulin binding domain (CaM-domain) increases baseline transmission while blocking STF and PHP. Mathematical modeling suggests that Ca2+/calmodulin/Unc13A interaction plastically stabilizes vesicle priming at release sites and that CaM-domain mutation causes constitutive stabilization, thereby blocking plasticity. Labeling the functionally essential Unc13A MUN domain reveals higher STED microscopy signals closer to release sites following CaM-domain mutation. Acute phorbol ester treatment similarly enhances NT release and blocks STF/PHP in synapses expressing wild-type Unc13A, while CaM-domain mutation occludes this, indicating common downstream effects. Thus, Unc13A regulatory domains integrate signals across timescales to switch release-site participation for synaptic plasticity.

AB - Presynaptic plasticity adjusts neurotransmitter (NT) liberation. Short-term facilitation (STF) tunes synapses to millisecond repetitive activation, while presynaptic homeostatic potentiation (PHP) of NT release stabilizes transmission over minutes. Despite different timescales of STF and PHP, our analysis of Drosophila neuromuscular junctions reveals functional overlap and shared molecular dependence on the release-site protein Unc13A. Mutating Unc13A's calmodulin binding domain (CaM-domain) increases baseline transmission while blocking STF and PHP. Mathematical modeling suggests that Ca2+/calmodulin/Unc13A interaction plastically stabilizes vesicle priming at release sites and that CaM-domain mutation causes constitutive stabilization, thereby blocking plasticity. Labeling the functionally essential Unc13A MUN domain reveals higher STED microscopy signals closer to release sites following CaM-domain mutation. Acute phorbol ester treatment similarly enhances NT release and blocks STF/PHP in synapses expressing wild-type Unc13A, while CaM-domain mutation occludes this, indicating common downstream effects. Thus, Unc13A regulatory domains integrate signals across timescales to switch release-site participation for synaptic plasticity.

KW - CP: Neuroscience

KW - neurotransmitter release sites

KW - presynaptic homeostatic potentiation

KW - short-term facilitation

KW - synaptic plasticity

KW - Unc13A

U2 - 10.1016/j.celrep.2023.112541

DO - 10.1016/j.celrep.2023.112541

M3 - Journal article

C2 - 37243591

AN - SCOPUS:85160063014

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

M1 - 112541

ER -

ID: 348164015