TY - JOUR
T1 - Signaling through Gsα is required for the growth and function of neuromuscular synapses in Drosophila
AU - Wolfgang, William J.
AU - Clay, Catherine
AU - Parker, Jacqueline
AU - Delgado, Ricardo
AU - Labarca, Pedro
AU - Kidokoro, Yoshiaki
AU - Forte, Michael
N1 - Funding Information:
The authors thank Drs. Philip Copenhaver and Sarah Smolik for critical review of the manuscript and Drs. Robert Renden and Kendal Broadie for communication of results before publication. This work was supported by grants from the National Institutes of Health (R01-NS42841; M.F.), from the Ministry of Education, Science, Sports and Culture of Japan (Y.K.), and Fondecyt (R.D. and P.L.). P.L. is an International Scholar of the Howard Hughes Medical Institute. CECS is a Millennium Science Institution.
PY - 2004/4/15
Y1 - 2004/4/15
N2 - Although synapses are assembled in a highly regulated fashion, synapses once formed are not static structures but continue to expand and retract throughout the life of an organism. One second messenger that has been demonstrated to play a critical role in synaptic growth and function is cAMP. Here, we have tested the idea that signaling through the heterotrimeric G protein, Gs, plays a coincident role with increases in intracellular Ca +2 in the regulation of adenylyl cyclases (ACs) during synaptic growth and in the function of synapses. In larvae containing a hypomorphic mutation in the dgs gene encoding the Drosophila Gsα protein, there is a significant decrease in the number of synaptic boutons and extent of synaptic arborization, as well as defects in the facilitation of synaptic transmission. Microscopic analysis confirmed that Gsα is localized at synapses both pre- and postsynaptically. Restricted expression of wild-type Gsα either pre- or postsynaptically rescued the mutational defects in bouton formation and defects in the facilitation of synaptic transmission, indicating that pathways activated by Gsα are likely to be involved in the reciprocal interactions between pre- and postsynaptic cells required for the development of mature synapses. In addition, this Gsα mutation interacted with fasII, dnc, and hyperexcitability mutants in a manner that revealed a coincident role for Gsα in the regulation of cAMP and FASII levels required during growth of these synapses. Our results demonstrate that Gsα-dependent signaling plays a role in the dynamic cellular reorganization that underlies synaptic growth.
AB - Although synapses are assembled in a highly regulated fashion, synapses once formed are not static structures but continue to expand and retract throughout the life of an organism. One second messenger that has been demonstrated to play a critical role in synaptic growth and function is cAMP. Here, we have tested the idea that signaling through the heterotrimeric G protein, Gs, plays a coincident role with increases in intracellular Ca +2 in the regulation of adenylyl cyclases (ACs) during synaptic growth and in the function of synapses. In larvae containing a hypomorphic mutation in the dgs gene encoding the Drosophila Gsα protein, there is a significant decrease in the number of synaptic boutons and extent of synaptic arborization, as well as defects in the facilitation of synaptic transmission. Microscopic analysis confirmed that Gsα is localized at synapses both pre- and postsynaptically. Restricted expression of wild-type Gsα either pre- or postsynaptically rescued the mutational defects in bouton formation and defects in the facilitation of synaptic transmission, indicating that pathways activated by Gsα are likely to be involved in the reciprocal interactions between pre- and postsynaptic cells required for the development of mature synapses. In addition, this Gsα mutation interacted with fasII, dnc, and hyperexcitability mutants in a manner that revealed a coincident role for Gsα in the regulation of cAMP and FASII levels required during growth of these synapses. Our results demonstrate that Gsα-dependent signaling plays a role in the dynamic cellular reorganization that underlies synaptic growth.
KW - Drosophila
KW - Gsα
KW - Signaling
KW - Synaptic growth
KW - cAMP
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U2 - 10.1016/j.ydbio.2004.01.007
DO - 10.1016/j.ydbio.2004.01.007
M3 - Article
C2 - 15063169
AN - SCOPUS:1942486375
SN - 0012-1606
VL - 268
SP - 295
EP - 311
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -