Cell Reports ( IF 8.8 ) Pub Date : 2020-07-07 , DOI: 10.1016/j.celrep.2020.107866 Tae Hee Han , Rosario Vicidomini , Cathy Isaura Ramos , Qi Wang , Peter Nguyen , Michal Jarnik , Chi-Hon Lee , Michal Stawarski , Roberto X. Hernandez , Gregory T. Macleod , Mihaela Serpe
Glutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation, and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and postsynaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology, and electrophysiology, we demonstrate that Neto-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptor field. In motor neurons (MNs), Neto-α controls neurotransmitter release in a KAR-dependent manner. In addition, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensures NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.
中文翻译:
Neto-α控制果蝇神经肌肉交界处的突触组织和体内平衡。
谷氨酸受体辅助蛋白控制受体的分布和功能,最终控制突触的组装,成熟和可塑性。在果蝇神经肌肉接头(NMJ),具有突触前和突触后的海藻酸盐型谷氨酸受体(KARs)的突触,我们显示辅助蛋白Neto进化出功能独特的同工型来调节突触的发育和体内平衡。使用遗传学,细胞生物学和电生理学,我们证明了Neto-α在NMJ的两侧均起作用。在肌肉中,Neto-α限制了突触后受体区域的大小。在运动神经元(MN)中,Neto-α以KAR依赖性方式控制神经递质的释放。另外,对于降低的突触后敏感性,神经递质释放的突触前增加既需要Neto-α,又足够。Neto-α的这种KAR独立功能与活动诱导的细胞基质重塑有关。我们建议果蝇 通过获取两个具有差异表达模式和活性的内托亚型来确保NMJ功能。