Haghighi A Pejmun, McCabe Brian D, Fetter Richard D, Palmer Jessica E, Hom Sabrina, Goodman Corey S
Life Sciences Addition, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Neuron. 2003 Jul 17;39(2):255-67. doi: 10.1016/s0896-6273(03)00427-6.
Retrograde signaling plays an important role in synaptic homeostasis, growth, and plasticity. A retrograde signal at the neuromuscular junction (NMJ) of Drosophila controls the homeostasis of neurotransmitter release. Here, we show that this retrograde signal is regulated by the postsynaptic activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII). Reducing CaMKII activity in muscles enhances the signal and increases neurotransmitter release, while constitutive activation of CaMKII in muscles inhibits the signal and decreases neurotransmitter release. Postsynaptic inhibition of CaMKII increases the number of presynaptic, vesicle-associated T bars at the active zones. Consistently, we show that glutamate receptor mutants also have a higher number of T bars; this increase is suppressed by postsynaptic activation of CaMKII. Furthermore, we demonstrate that presynaptic BMP receptor wishful thinking is required for the retrograde signal to function. Our results indicate that CaMKII plays a key role in the retrograde control of homeostasis of synaptic transmission at the NMJ of Drosophila.
逆行信号传导在突触稳态、生长和可塑性中发挥着重要作用。果蝇神经肌肉接头（NMJ）处的逆行信号控制着神经递质释放的稳态。在此，我们表明这种逆行信号受钙/钙调蛋白依赖性蛋白激酶II（CaMKII）的突触后活性调节。降低肌肉中的CaMKII活性会增强该信号并增加神经递质释放，而肌肉中CaMKII的组成型激活则会抑制该信号并减少神经递质释放。对CaMKII的突触后抑制会增加活性区突触前、与囊泡相关的T形结构的数量。同样，我们表明谷氨酸受体突变体也有更多的T形结构；这种增加被CaMKII的突触后激活所抑制。此外，我们证明逆行信号发挥作用需要突触前BMP受体“如意算盘”。我们的结果表明，CaMKII在果蝇NMJ处突触传递稳态的逆行控制中起关键作用。
