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Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling. / Böhme, Mathias A.; Beis, Christina; Reddy-Alla, Suneel et al.
In: Nature Neuroscience, Vol. 19, No. 10, 01.10.2016, p. 1311-1320.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Böhme, MA, Beis, C, Reddy-Alla, S, Reynolds, E, Mampell, MM, Grasskamp, AT, Lützkendorf, J, Bergeron, DD, Driller, JH, Babikir, H, Göttfert, F, Robinson, IM, O'Kane, CJ, Hell, SW, Wahl, MC, Stelzl, U, Loll, B, Walter, AM & Sigrist, SJ 2016, 'Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling', Nature Neuroscience, vol. 19, no. 10, pp. 1311-1320. https://doi.org/10.1038/nn.4364

APA

Böhme, M. A., Beis, C., Reddy-Alla, S., Reynolds, E., Mampell, M. M., Grasskamp, A. T., Lützkendorf, J., Bergeron, D. D., Driller, J. H., Babikir, H., Göttfert, F., Robinson, I. M., O'Kane, C. J., Hell, S. W., Wahl, M. C., Stelzl, U., Loll, B., Walter, A. M., & Sigrist, S. J. (2016). Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling. Nature Neuroscience, 19(10), 1311-1320. https://doi.org/10.1038/nn.4364

Vancouver

Böhme MA, Beis C, Reddy-Alla S, Reynolds E, Mampell MM, Grasskamp AT et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling. Nature Neuroscience. 2016 Oct 1;19(10):1311-1320. Epub 2016 Aug 15. doi: 10.1038/nn.4364

Author

Böhme, Mathias A. ; Beis, Christina ; Reddy-Alla, Suneel et al. / Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling. In: Nature Neuroscience. 2016 ; Vol. 19, No. 10. pp. 1311-1320.

Bibtex

@article{df294a906ccb44ac95a1beedc8cf5db8,
title = "Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling",
abstract = "Brain function relies on fast and precisely timed synaptic vesicle (SV) release at active zones (AZs). Efficacy of SV release depends on distance from SV to Ca2+ channel, but molecular mechanisms controlling this are unknown. Here we found that distances can be defined by targeting two unc-13 (Unc13) isoforms to presynaptic AZ subdomains. Super-resolution and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-α, and Unc13A was positioned by Bruchpilot and Rim-binding protein complexes at maturing AZs. Unc13B localized 120 nm away from Ca2+ channels, whereas Unc13A localized only 70 nm away and was responsible for docking SVs at this distance. Unc13A null mutants suffered from inefficient, delayed and EGTA-supersensitive release. Mathematical modeling suggested that synapses normally operate via two independent release pathways differentially positioned by either isoform. We identified isoform-specific Unc13-AZ scaffold interactions regulating SV-Ca2+ -channel topology whose developmental tightening optimizes synaptic transmission.",
author = "B{\"o}hme, {Mathias A.} and Christina Beis and Suneel Reddy-Alla and Eric Reynolds and Mampell, {Malou M.} and Grasskamp, {Andreas T.} and Janine L{\"u}tzkendorf and Bergeron, {Dominique Dufour} and Driller, {Jan H.} and Husam Babikir and Fabian G{\"o}ttfert and Robinson, {Iain M.} and O'Kane, {Cahir J.} and Hell, {Stefan W.} and Wahl, {Markus C.} and Ulrich Stelzl and Bernhard Loll and Walter, {Alexander M.} and Sigrist, {Stephan J.}",
note = "Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",
year = "2016",
month = oct,
day = "1",
doi = "10.1038/nn.4364",
language = "English",
volume = "19",
pages = "1311--1320",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Research",
number = "10",

}

RIS

TY - JOUR

T1 - Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling

AU - Böhme, Mathias A.

AU - Beis, Christina

AU - Reddy-Alla, Suneel

AU - Reynolds, Eric

AU - Mampell, Malou M.

AU - Grasskamp, Andreas T.

AU - Lützkendorf, Janine

AU - Bergeron, Dominique Dufour

AU - Driller, Jan H.

AU - Babikir, Husam

AU - Göttfert, Fabian

AU - Robinson, Iain M.

AU - O'Kane, Cahir J.

AU - Hell, Stefan W.

AU - Wahl, Markus C.

AU - Stelzl, Ulrich

AU - Loll, Bernhard

AU - Walter, Alexander M.

AU - Sigrist, Stephan J.

N1 - Publisher Copyright: © 2016 Nature America, Inc.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Brain function relies on fast and precisely timed synaptic vesicle (SV) release at active zones (AZs). Efficacy of SV release depends on distance from SV to Ca2+ channel, but molecular mechanisms controlling this are unknown. Here we found that distances can be defined by targeting two unc-13 (Unc13) isoforms to presynaptic AZ subdomains. Super-resolution and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-α, and Unc13A was positioned by Bruchpilot and Rim-binding protein complexes at maturing AZs. Unc13B localized 120 nm away from Ca2+ channels, whereas Unc13A localized only 70 nm away and was responsible for docking SVs at this distance. Unc13A null mutants suffered from inefficient, delayed and EGTA-supersensitive release. Mathematical modeling suggested that synapses normally operate via two independent release pathways differentially positioned by either isoform. We identified isoform-specific Unc13-AZ scaffold interactions regulating SV-Ca2+ -channel topology whose developmental tightening optimizes synaptic transmission.

AB - Brain function relies on fast and precisely timed synaptic vesicle (SV) release at active zones (AZs). Efficacy of SV release depends on distance from SV to Ca2+ channel, but molecular mechanisms controlling this are unknown. Here we found that distances can be defined by targeting two unc-13 (Unc13) isoforms to presynaptic AZ subdomains. Super-resolution and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-α, and Unc13A was positioned by Bruchpilot and Rim-binding protein complexes at maturing AZs. Unc13B localized 120 nm away from Ca2+ channels, whereas Unc13A localized only 70 nm away and was responsible for docking SVs at this distance. Unc13A null mutants suffered from inefficient, delayed and EGTA-supersensitive release. Mathematical modeling suggested that synapses normally operate via two independent release pathways differentially positioned by either isoform. We identified isoform-specific Unc13-AZ scaffold interactions regulating SV-Ca2+ -channel topology whose developmental tightening optimizes synaptic transmission.

U2 - 10.1038/nn.4364

DO - 10.1038/nn.4364

M3 - Journal article

C2 - 27526206

AN - SCOPUS:84982166075

VL - 19

SP - 1311

EP - 1320

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 10

ER -