Signaling through Gs alpha is required for the growth and function of neuromuscular synapses in Drosophila.
Signaling through Gs alpha is required for the growth and function of neuromuscular synapses in Drosophila.
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DOI：
10.1016/j.ydbio.2004.01.007
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发表时间：
2004-04
影响因子：
2.7
通讯作者：
W. Wolfgang;Catherine Clay;J. Parker;R. Delgado;P. Labarca;Y. Kidokoro;M. Forte
中科院分区：
文献类型：
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作者：
W. Wolfgang;Catherine Clay;J. Parker;R. Delgado;P. Labarca;Y. Kidokoro;M. Forte
虽然突触是以高度调节的方式组装的，但突触一旦形成就不是静态结构，而是在生物体的整个生命过程中持续扩张和收缩。已经证明在突触生长和功能中起关键作用的第二信使是cAMP。在这里，我们已经测试的想法，信号通过异源三聚体G蛋白，Gs，起着一致的作用，细胞内Ca+2在调节腺苷酸环化酶（AC）在突触生长和突触的功能。在编码果蝇Gsα蛋白的dgs基因中含有亚型突变的幼虫中，突触终扣的数量和突触树枝化的程度显著减少，并且突触传递的便利化缺陷。显微镜分析证实Gsα定位于突触前和突触后。限制性表达的野生型Gsα在突触前或突触后挽救了突变缺陷的形成和缺陷的促进突触传递，表明Gsα激活的途径可能参与了相互作用的突触前和突触后细胞之间所需的成熟突触的发展。此外，该Gsα突变与fasII、dnc和超兴奋性突变体相互作用的方式揭示了Gsα在这些突触生长期间所需的cAMP和FASII水平的调节中的一致作用。我们的研究结果表明，Gsα依赖性信号在突触生长的基础上的动态细胞重组中发挥作用。
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+2in 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.