Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

Kwun-Nok Mimi Man; Cordelia Imig; Alexander M Walter; Paulo César da Silva Pinheiro; David R Stevens; Jens Rettig; Jakob B Sørensen; Benjamin H Cooper; Nils Brose; Sonja M Wojcik

doi:10.7554/eLife.10635

Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

Kwun-Nok Mimi Man, Cordelia Imig, Alexander M Walter, Paulo César da Silva Pinheiro, David R Stevens, Jens Rettig, Jakob B Sørensen, Benjamin H Cooper, Nils Brose, Sonja M Wojcik

Neuronal Signalling

30 Citations (Scopus)

Abstract

It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca²⁺-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.

Original language	English
Article number	e10635
Journal	eLife
Volume	4
Pages (from-to)	1-28
Number of pages	28
ISSN	2050-084X
DOIs	https://doi.org/10.7554/eLife.10635
Publication status	Published - 17 Nov 2015

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@article{594c4f5f031a448694ee15b15992d131,

title = "Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis",

abstract = "It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca2+-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.",

author = "Man, {Kwun-Nok Mimi} and Cordelia Imig and Walter, {Alexander M} and {da Silva Pinheiro}, {Paulo C{\'e}sar} and Stevens, {David R} and Jens Rettig and S{\o}rensen, {Jakob B} and Cooper, {Benjamin H} and Nils Brose and Wojcik, {Sonja M}",

year = "2015",

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doi = "10.7554/eLife.10635",

language = "English",

volume = "4",

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journal = "eLife",

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T1 - Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

AU - Man, Kwun-Nok Mimi

AU - Imig, Cordelia

AU - Walter, Alexander M

AU - da Silva Pinheiro, Paulo César

AU - Stevens, David R

AU - Rettig, Jens

AU - Sørensen, Jakob B

AU - Cooper, Benjamin H

AU - Brose, Nils

AU - Wojcik, Sonja M

PY - 2015/11/17

Y1 - 2015/11/17

N2 - It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca2+-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.

AB - It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca2+-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.

U2 - 10.7554/eLife.10635

DO - 10.7554/eLife.10635

M3 - Journal article

C2 - 26575293

SN - 2050-084X

VL - 4

SP - 1

EP - 28

JO - eLife

JF - eLife

M1 - e10635

ER -

Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

Abstract

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