β phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs

被引：382

作者：

Rhee, JS

Betz, A

Pyott, S

Reim, K

Varoqueaux, F

Augustin, I

Hesse, D

Südhof, TC

Takahashi, M

Rosenmund, C

Brose, N

机构：

[1] Max Planck Inst Biophys Chem, Abt Membranbiophys, D-37077 Gottingen, Germany

[2] Max Planck Inst Expt Med, Abt Mol Neurobiol, D-37075 Gottingen, Germany

[3] Max Planck Inst Expt Med, Abt Neurogenet, D-37075 Gottingen, Germany

[4] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Ctr Basic Neurosci,Dept Mol Genet, Dallas, TX 75390 USA

[5] Mitsubishi Kasei Inst Life Sci, Tokyo 1948511, Japan

来源：

CELL | 2002年 / 108卷 / 01期

关键词：

D O I：

10.1016/S0092-8674(01)00635-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C-1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C-1 domain is essential for use-dependent alterations of synaptic efficacy and survival.

引用

页码：121 / 133

页数：13

共 48 条

[1] Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells
Ashery, U
Varoqueaux, F
Voets, T
Betz, A
Thakur, P
Koch, H
Neher, E
Brose, N
Rettig, J
[J]. EMBO JOURNAL, 2000, 19 (14) : 3586 - 3596
[2] Differential expression of two novel Munc13 proteins in rat brain
Augustin, I
Betz, A
Herrmann, C
Jo, T
Brose, N
[J]. BIOCHEMICAL JOURNAL, 1999, 337 : 363 - 371
[3] The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice
Augustin, I
Korte, S
Rickmann, M
Kretzschmar, HA
Südhof, TC
Herms, JW
Brose, N
[J]. JOURNAL OF NEUROSCIENCE, 2001, 21 (01) : 10 - 17
[4] Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles
Augustin, I
Rosenmund, C
Südhof, TC
Brose, N
[J]. NATURE, 1999, 400 (6743) : 457 - 461
[5] EXCITATORY AND INHIBITORY AUTAPTIC CURRENTS IN ISOLATED HIPPOCAMPAL-NEURONS MAINTAINED IN CELL-CULTURE
BEKKERS, JM
STEVENS, CF
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) : 7834 - 7838
[6] Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming
Betz, A
Thakur, P
Junge, HJ
Ashery, U
Rhee, JS
Scheuss, V
Rosenmund, C
Rettig, J
Brose, N
[J]. NEURON, 2001, 30 (01) : 183 - 196
[7] Betz A, 1997, J BIOL CHEM, V272, P2520
[8] Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release
Betz, A
Ashery, U
Rickmann, M
Augustin, I
Neher, E
Südhof, TC
Rettig, J
Brose, N
[J]. NEURON, 1998, 21 (01) : 123 - 136
[9] MAMMALIAN HOMOLOGS OF CAENORHABDITIS-ELEGANS UNC-13 GENE DEFINE NOVEL FAMILY OF C-2-DOMAIN PROTEINS
BROSE, N
HOFMANN, K
HATA, Y
SUDHOF, TC
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) : 25273 - 25280
[10] Regulation of transmitter release by Unc-13 and its homologues
Brose, N
Rosenmund, C
Rettig, J
[J]. CURRENT OPINION IN NEUROBIOLOGY, 2000, 10 (03) : 303 - 311

← 1 2 3 4 5 →