Facilitation of synaptic transmission by EGL-30 Gqα and EGL-8 PLCβ:: DAG binding to UNC-13 is required to stimulate acetylcholine release

被引:256
作者
Lackner, MR [1 ]
Nurrish, SJ [1 ]
Kaplan, JM [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1016/S0896-6273(00)80848-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We show that neurotransmitter release at Caenorhabditis elegans neuromuscular junctions is facilitated by a presynaptic pathway composed of a G(q)alpha (EGL-30), EGL-8 phospholipase C beta (PLC beta), and the diacylglycerol- (DAG-) binding protein UNC-13. Activation of this pathway increased release of acetylcholine at neuromuscular junctions, whereas inactivation decreased release. Phorbol esters stimulated acetylcholine release, and this effect was blocked by a mutation that eliminates phorbol ester binding to UNC-13. Expression of a constitutively membrane-bound form of UNC-13 restored acetylcholine release to mutants lacking the egl-8 PLC beta. Activation of this pathway with muscarinic agonists caused UNC-13 to accumulate in punctate structures in the ventral nerve cord. These results suggest that presynaptic DAG facilitates synaptic transmission and that part of this effect is mediated by UNC-13.
引用
收藏
页码:335 / 346
页数:12
相关论文
共 58 条
[1]   THE CAENORHABDITIS-ELEGANS UNC-13 GENE-PRODUCT IS A PHOSPHOLIPID-DEPENDENT HIGH-AFFINITY PHORBOL ESTER RECEPTOR [J].
AHMED, S ;
MARUYAMA, IN ;
KOZMA, R ;
LEE, J ;
BRENNER, S ;
LIM, L .
BIOCHEMICAL JOURNAL, 1992, 287 :995-999
[2]   THE CAENORHABDITIS-ELEGANS UNC-17 GENE - A PUTATIVE VESICULAR ACETYLCHOLINE TRANSPORTER [J].
ALFONSO, A ;
GRUNDAHL, K ;
DUERR, JS ;
HAN, HP ;
RAND, JB .
SCIENCE, 1993, 261 (5121) :617-619
[3]   MODULATION OF VERTEBRATE NEURONAL CALCIUM CHANNELS BY TRANSMITTERS [J].
ANWYL, R .
BRAIN RESEARCH REVIEWS, 1991, 16 (03) :265-281
[4]   Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles [J].
Augustin, I ;
Rosenmund, C ;
Südhof, TC ;
Brose, N .
NATURE, 1999, 400 (6743) :457-461
[5]  
Betz A, 1997, J BIOL CHEM, V272, P2520
[6]   Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release [J].
Betz, A ;
Ashery, U ;
Rickmann, M ;
Augustin, I ;
Neher, E ;
Südhof, TC ;
Rettig, J ;
Brose, N .
NEURON, 1998, 21 (01) :123-136
[7]  
BRENNER S, 1974, GENETICS, V77, P71
[8]   Mutations in a C-elegans G(q)alpha gene disrupt movement, egg laying, and viability [J].
Brundage, L ;
Avery, L ;
Katz, A ;
Kim, UJ ;
Mendel, JE ;
Sternberg, PW ;
Simon, MI .
NEURON, 1996, 16 (05) :999-1009
[9]   Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL [J].
Chyb, S ;
Raghu, P ;
Hardie, RC .
NATURE, 1999, 397 (6716) :255-259
[10]  
Colbert HA, 1997, J NEUROSCI, V17, P8259