A genetic analysis of synaptic development:: Pre- and postsynaptic dCBP control transmitter release at the Drosophila NMJ

被引:39
作者
Marek, KW
Ng, N
Fetter, R
Smolik, S
Goodman, CS
Davis, GW [1 ]
机构
[1] Univ Calif San Francisco, Sch Med, Dept Biochem & Biophys, Cell Biol Program, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Sch Med, Dept Biochem & Biophys, Program Neurosci, San Francisco, CA 94143 USA
[3] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[4] Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA
关键词
D O I
10.1016/S0896-6273(00)81058-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Postsynaptic dCBP (Drosophila homolog of the CREB binding protein) is required for presynaptic functional development. Viable, hypomorphic dCBP mutations have a similar to 50% reduction in presynaptic transmitter release without altering the Ca2+ cooperativity of release or synaptic ultrastructure (total bouton number is increased by 25%-30%). Exogenous expression of dCBP in muscle rescues impaired presynaptic release in the dCBP mutant background, while presynaptic dCBP expression does not. In addition, overexpression experiments indicate that elevated dCBP can also inhibit presynaptic functional development in a manner distinct from the effects of dCBP loss of function. Pre- or postsynaptic overexpression of dCBP (in wild type) reduces presynaptic release. However, we do not observe an increase in bouton number, and presynaptic overexpression impairs short-term facilitation. These data suggest that dCBP participates in a postsynaptic regulatory system that controls functional synaptic development.
引用
收藏
页码:537 / 547
页数:11
相关论文
共 42 条
[1]   Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling [J].
Akimaru, H ;
Chen, Y ;
Dai, P ;
Hou, DX ;
Nonaka, M ;
Smolik, SM ;
Armstrong, S ;
Goodman, RH ;
Ishii, S .
NATURE, 1997, 386 (6626) :735-738
[2]   Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons [J].
Arancio, O ;
Kiebler, M ;
Lee, CJ ;
LevRam, V ;
Tsien, RY ;
Kandel, ER ;
Hawkins, RD .
CELL, 1996, 87 (06) :1025-1035
[3]   APLYSIA CREB2 REPRESSES LONG-TERM FACILITATION - RELIEF OF REPRESSION CONVERTS TRANSIENT FACILITATION INTO LONG-TERM FUNCTIONAL AND STRUCTURAL-CHANGE [J].
BARTSCH, D ;
GHIRARDI, M ;
SKEHEL, PA ;
KARL, KA ;
HERDER, SP ;
CHEN, M ;
BAILEY, CH ;
KANDEL, ER .
CELL, 1995, 83 (06) :979-992
[4]   CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation [J].
Bartsch, D ;
Casadio, A ;
Karl, KA ;
Serodio, P ;
Kandel, ER .
CELL, 1998, 95 (02) :211-223
[5]   CREB phosphorylation and dephosphorylation: A Ca2(+)- and stimulus duration-dependent switch for hippocampal gene expression [J].
Bito, H ;
Deisseroth, K ;
Tsien, RW .
CELL, 1996, 87 (07) :1203-1214
[6]   A SYNAPTIC MODEL OF MEMORY - LONG-TERM POTENTIATION IN THE HIPPOCAMPUS [J].
BLISS, TVP ;
COLLINGRIDGE, GL .
NATURE, 1993, 361 (6407) :31-39
[7]   DEFICIENT LONG-TERM-MEMORY IN MICE WITH A TARGETED MUTATION OF THE CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN [J].
BOURTCHULADZE, R ;
FRENGUELLI, B ;
BLENDY, J ;
CIOFFI, D ;
SCHUTZ, G ;
SILVA, AJ .
CELL, 1994, 79 (01) :59-68
[8]   Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses [J].
Buchs, PA ;
Muller, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :8040-8045
[9]   A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis [J].
Casadio, A ;
Martin, KC ;
Giustetto, M ;
Zhu, HX ;
Chen, M ;
Bartsch, D ;
Bailey, CH ;
Kandel, ER .
CELL, 1999, 99 (02) :221-237
[10]   PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP [J].
CHRIVIA, JC ;
KWOK, RPS ;
LAMB, N ;
HAGIWARA, M ;
MONTMINY, MR ;
GOODMAN, RH .
NATURE, 1993, 365 (6449) :855-859