Schmid Andreas, Qin Gang, Wichmann Carolin, Kittel Robert J, Mertel Sara, Fouquet Wernher, Schmidt Manuela, Heckmann Manfred, Sigrist Stephan J
European Neuroscience Institute Göttingen, 37077 Göttingen, Germany.
J Neurosci. 2006 Nov 1;26(44):11267-77. doi: 10.1523/JNEUROSCI.2722-06.2006.
The assembly of glutamatergic postsynaptic densities (PSDs) seems to involve the gradual recruitment of molecular components from diffuse cellular pools. Whether the glutamate receptors themselves are needed to instruct the structural and molecular assembly of the PSD has hardly been addressed. Here, we engineered Drosophila neuromuscular junctions (NMJs) to express none or only drastically reduced amounts of their postsynaptic non-NMDA-type glutamate receptors. At such NMJs, principal synapse formation proceeded and presynaptic active zones showed normal composition and ultrastructure as well as proper glutamate release. At the postsynaptic site, initial steps of molecular and structural assembly took place as well. However, growth of the nascent PSDs to mature size was inhibited, and proteins normally excluded from PSD membranes remained at these apparently immature sites. Intriguingly, synaptic transmission as well as glutamate binding to glutamate receptors appeared dispensable for synapse maturation. Thus, our data suggest that incorporation of non-NMDA-type glutamate receptors and likely their protein-protein interactions with additional PSD components triggers a conversion from an initial to a mature stage of PSD assembly.
谷氨酸能突触后致密物（PSD）的组装似乎涉及从弥散的细胞池中逐渐招募分子成分。谷氨酸受体本身是否需要指导PSD的结构和分子组装几乎未得到探讨。在这里，我们改造了果蝇神经肌肉接头（NMJ），使其不表达或仅大量减少其突触后非NMDA型谷氨酸受体。在这样的NMJ中，主要突触形成继续进行，突触前活性区显示出正常的组成和超微结构以及适当的谷氨酸释放。在突触后位点，分子和结构组装的初始步骤也发生了。然而，新生PSD生长到成熟大小受到抑制，通常被排除在PSD膜之外的蛋白质仍留在这些明显不成熟的位点。有趣的是，突触传递以及谷氨酸与谷氨酸受体的结合似乎对于突触成熟是可有可无的。因此，我们的数据表明，非NMDA型谷氨酸受体的纳入以及它们与其他PSD成分的蛋白质-蛋白质相互作用可能触发了PSD组装从初始阶段到成熟阶段的转变。
