Neuroscience Research Institute and Department of Cellular Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Neuron. 2009 Dec 24;64(6):871-84. doi: 10.1016/j.neuron.2009.11.023.
Persistent changes in synaptic strength are locally regulated by both protein degradation and synthesis; however, the coordination of these opposing limbs is poorly understood. Here, we found that the RISC protein MOV10 was present at synapses and was rapidly degraded by the proteasome in an NMDA-receptor-mediated activity-dependent manner. We designed a translational trap to capture those mRNAs whose spatiotemporal translation is regulated by MOV10. When MOV10 was suppressed, a set of mRNAs--including alpha-CaMKII, Limk1, and the depalmitoylating enzyme lysophospholipase1 (Lypla1)--selectively entered the polysome compartment. We also observed that Lypla1 mRNA is associated with the brain-enriched microRNA miR-138. Using a photoconvertible translation reporter, Kaede, we analyzed the activity-dependent protein synthesis driven by Lypla1 and alpha-CaMKII 3'UTRs. We established this protein synthesis to be MOV10 and proteasome dependent. These results suggest a unifying picture of a local translational regulatory mechanism during synaptic plasticity.
突触强度的持续变化受蛋白质降解和合成的局部调节；然而，这些对立分支的协调尚不清楚。在这里，我们发现 RISC 蛋白 MOV10 存在于突触中，并在 NMDA 受体介导的活性依赖性方式下被蛋白酶体快速降解。我们设计了一种翻译陷阱来捕获那些由 MOV10 调节时空翻译的 mRNA。当 MOV10 被抑制时，一组 mRNA——包括 alpha-CaMKII、Limk1 和去棕榈酰化酶溶脂酶 1 (Lypla1)——选择性进入多核糖体区室。我们还观察到 Lypla1 mRNA 与富含大脑的 microRNA miR-138 相关。使用光转化翻译报告基因 Kaede，我们分析了 Lypla1 和 alpha-CaMKII 3'UTR 驱动的活性依赖性蛋白质合成。我们确定这种蛋白质合成依赖于 MOV10 和蛋白酶体。这些结果提出了一个统一的局部翻译调节机制在突触可塑性过程中的图片。
