Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission

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

Standard

Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. / Reddy-Alla, Suneel; Böhme, Mathias A; Reynolds, Eric; Beis, Christina; Grasskamp, Andreas T; Mampell, Malou M; Maglione, Marta; Jusyte, Meida; Rey, Ulises; Babikir, Husam; McCarthy, Anthony W; Quentin, Christine; Matkovic, Tanja; Bergeron, Dominique Dufour; Mushtaq, Zeeshan; Göttfert, Fabian; Owald, David; Mielke, Thorsten; Hell, Stefan W; Sigrist, Stephan J; Walter, Alexander M.

In: Neuron, Vol. 95, No. 6, 2017, p. 1350-1364.

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

Harvard

Reddy-Alla, S, Böhme, MA, Reynolds, E, Beis, C, Grasskamp, AT, Mampell, MM, Maglione, M, Jusyte, M, Rey, U, Babikir, H, McCarthy, AW, Quentin, C, Matkovic, T, Bergeron, DD, Mushtaq, Z, Göttfert, F, Owald, D, Mielke, T, Hell, SW, Sigrist, SJ & Walter, AM 2017, 'Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission', Neuron, vol. 95, no. 6, pp. 1350-1364. https://doi.org/10.1016/j.neuron.2017.08.016

APA

Reddy-Alla, S., Böhme, M. A., Reynolds, E., Beis, C., Grasskamp, A. T., Mampell, M. M., Maglione, M., Jusyte, M., Rey, U., Babikir, H., McCarthy, A. W., Quentin, C., Matkovic, T., Bergeron, D. D., Mushtaq, Z., Göttfert, F., Owald, D., Mielke, T., Hell, S. W., ... Walter, A. M. (2017). Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. Neuron, 95(6), 1350-1364. https://doi.org/10.1016/j.neuron.2017.08.016

Vancouver

Reddy-Alla S, Böhme MA, Reynolds E, Beis C, Grasskamp AT, Mampell MM et al. Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. Neuron. 2017;95(6):1350-1364. https://doi.org/10.1016/j.neuron.2017.08.016

Author

Reddy-Alla, Suneel ; Böhme, Mathias A ; Reynolds, Eric ; Beis, Christina ; Grasskamp, Andreas T ; Mampell, Malou M ; Maglione, Marta ; Jusyte, Meida ; Rey, Ulises ; Babikir, Husam ; McCarthy, Anthony W ; Quentin, Christine ; Matkovic, Tanja ; Bergeron, Dominique Dufour ; Mushtaq, Zeeshan ; Göttfert, Fabian ; Owald, David ; Mielke, Thorsten ; Hell, Stefan W ; Sigrist, Stephan J ; Walter, Alexander M. / Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. In: Neuron. 2017 ; Vol. 95, No. 6. pp. 1350-1364.

Bibtex

@article{c3df8f4089154fe49ad9b5b1f1a4c1fe,

title = "Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission",

abstract = "Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging of Drosophila neuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release.",

keywords = "Animals, Carrier Proteins/metabolism, Drosophila, Exocytosis/physiology, Neuromuscular Junction/metabolism, Synaptic Transmission/physiology, Synaptic Vesicles/metabolism",

author = "Suneel Reddy-Alla and B{\"o}hme, {Mathias A} and Eric Reynolds and Christina Beis and Grasskamp, {Andreas T} and Mampell, {Malou M} and Marta Maglione and Meida Jusyte and Ulises Rey and Husam Babikir and McCarthy, {Anthony W} and Christine Quentin and Tanja Matkovic and Bergeron, {Dominique Dufour} and Zeeshan Mushtaq and Fabian G{\"o}ttfert and David Owald and Thorsten Mielke and Hell, {Stefan W} and Sigrist, {Stephan J} and Walter, {Alexander M}",

year = "2017",

doi = "10.1016/j.neuron.2017.08.016",

language = "English",

volume = "95",

pages = "1350--1364",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission

AU - Reddy-Alla, Suneel

AU - Böhme, Mathias A

AU - Reynolds, Eric

AU - Beis, Christina

AU - Grasskamp, Andreas T

AU - Mampell, Malou M

AU - Maglione, Marta

AU - Jusyte, Meida

AU - Rey, Ulises

AU - Babikir, Husam

AU - McCarthy, Anthony W

AU - Quentin, Christine

AU - Matkovic, Tanja

AU - Bergeron, Dominique Dufour

AU - Mushtaq, Zeeshan

AU - Göttfert, Fabian

AU - Owald, David

AU - Mielke, Thorsten

AU - Hell, Stefan W

AU - Sigrist, Stephan J

AU - Walter, Alexander M

PY - 2017

Y1 - 2017

N2 - Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging of Drosophila neuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release.

AB - Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging of Drosophila neuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release.

KW - Animals

KW - Carrier Proteins/metabolism

KW - Drosophila

KW - Exocytosis/physiology

KW - Neuromuscular Junction/metabolism

KW - Synaptic Transmission/physiology

KW - Synaptic Vesicles/metabolism

U2 - 10.1016/j.neuron.2017.08.016

DO - 10.1016/j.neuron.2017.08.016

M3 - Journal article

C2 - 28867551

VL - 95

SP - 1350

EP - 1364

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -

ID: 334034941

Department of Neuroscience