Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory
Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory
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DOI：
10.1016/j.cell.2012.01.004
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发表时间：
2012-02-03
期刊：
影响因子：
64.5
通讯作者：
Si, Kausik
中科院分区：
文献类型：
--
作者：
Majumdar, Amitabha;Cesario, Wanda Colon;Si, Kausik
长期记忆研究中的一个长期问题是，当启动这一过程的蛋白质在几天内翻转并消失时，记忆痕迹如何持续多年。此前，我们假设胞浆多聚腺苷化元件结合蛋白(CPEB)的自持性淀粉样变寡聚体(CPEB)为维持活性依赖的突触变化提供了一种机制，从而维持记忆的持久性。在这里，我们发现果蝇CPEB Orb2形成淀粉样寡聚体，并且寡聚体富含在突触膜组分中。在Orb2的两种蛋白质异构体中，类淀粉样寡聚体的形成依赖于Orb2A型。Orb2a蛋白样域中的点突变减少了Orb2的淀粉样寡聚化，但不会干扰持续24小时的学习或记忆。然而，突变果蝇未能使记忆稳定超过48小时。这些结果支持这样的观点，即神经元CPEB的淀粉样寡聚体对长期记忆的持久性至关重要。
A long-standing question in the study of long-term memory is how a memory trace persists for years when the proteins that initiated the process turn over and disappear within days. Previously, we postulated that self-sustaining amyloidogenic oligomers of cytoplasmic polyadenylation elementbinding protein (CPEB) provide a mechanism for the maintenance of activity-dependent synaptic changes and, thus, the persistence of memory. Here, we found that the Drosophila CPEB Orb2 forms amyloid-like oligomers, and oligomers are enriched in the synaptic membrane fraction. Of the two protein isoforms of Orb2, the amyloid-like oligomer formation is dependent on the Orb2A form. A point mutation in the prion-like domain of Orb2A, which reduced amyloid-like oligomerization of Orb2, did not interfere with learning or memory persisting up to 24 hr. However the mutant flies failed to stabilize memory beyond 48 hr. These results support the idea that amyloid-like oligomers of neuronal CPEB are critical for the persistence of long-term memory.