Goold Carleton P, Davis Graeme W
Department of Biochemistry and Biophysics, Program in Neuroscience, University of California San Francisco, San Francisco, CA 94158-2822, USA.
Neuron. 2007 Oct 4;56(1):109-23. doi: 10.1016/j.neuron.2007.08.006.
Inhibition of postsynaptic glutamate receptors at the Drosophila NMJ initiates a compensatory increase in presynaptic release termed synaptic homeostasis. BMP signaling is necessary for normal synaptic growth and stability. It remains unknown whether BMPs have a specific role during synaptic homeostasis and, if so, whether BMP signaling functions as an instructive retrograde signal that directly modulates presynaptic transmitter release. Here, we demonstrate that the BMP receptor (Wit) and ligand (Gbb) are necessary for the rapid induction of synaptic homeostasis. We also provide evidence that both Wit and Gbb have functions during synaptic homeostasis that are separable from NMJ growth. However, further genetic experiments demonstrate that Gbb does not function as an instructive retrograde signal during synaptic homeostasis. Rather, our data indicate that Wit and Gbb function via the downstream transcription factor Mad and that Mad-mediated signaling is continuously required during development to confer competence of motoneurons to express synaptic homeostasis.
抑制果蝇神经肌肉接头处的突触后谷氨酸受体,会引发突触前释放的代偿性增加,即所谓的突触稳态。骨形态发生蛋白(BMP)信号传导对于正常的突触生长和稳定性是必需的。BMPs在突触稳态过程中是否具有特定作用,以及如果有作用,BMP信号传导是否作为一种指导性逆行信号直接调节突触前递质释放,目前仍不清楚。在这里,我们证明BMP受体(Wit)和配体(Gbb)对于快速诱导突触稳态是必需的。我们还提供证据表明,Wit和Gbb在突触稳态过程中具有与神经肌肉接头生长可分离的功能。然而,进一步的遗传学实验表明,Gbb在突触稳态过程中不作为指导性逆行信号发挥作用。相反,我们的数据表明,Wit和Gbb通过下游转录因子Mad发挥作用,并且在发育过程中持续需要Mad介导的信号传导,以使运动神经元具备表达突触稳态的能力。