Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis
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Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis. / Man, Kwun-Nok Mimi; Imig, Cordelia; Walter, Alexander M; da Silva Pinheiro, Paulo César; Stevens, David R; Rettig, Jens; Sørensen, Jakob B; Cooper, Benjamin H; Brose, Nils; Wojcik, Sonja M.
In: eLife, Vol. 4, e10635, 17.11.2015, p. 1-28.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
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
VL - 4
SP - 1
EP - 28
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e10635
ER -
ID: 148102260