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Dlg 对于短期记忆是必需的,并与大脑中的 NMDA 受体相互作用。

Dlg Is Required for Short-Term Memory and Interacts with NMDAR in the Brain.

机构信息

Department of Neuroscience and Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.

出版信息

Int J Mol Sci. 2022 Aug 16;23(16):9187. doi: 10.3390/ijms23169187.

Abstract

The vertebrates' scaffold proteins of the Dlg-MAGUK family are involved in the recruitment, clustering, and anchoring of glutamate receptors to the postsynaptic density, particularly the NMDA subtype glutamate-receptors (NRs), necessary for long-term memory and LTP. In , the only gene of the subfamily generates two main products, , broadly expressed, and , restricted to the nervous system. In the brain, NRs are expressed in the adult brain and are involved in memory, however, the role of Dlg in these processes and its relationship with NRs has been scarcely explored. Here, we show that the mutants display defects in short-term memory in the olfactory associative-learning paradigm. These defects are dependent on the presence of DlgS97 in the Mushroom Body (MB) synapses. Moreover, Dlg is immunoprecipitated with NRs in the adult brain. Dlg is also expressed in the larval neuromuscular junction (NMJ) pre and post-synaptically and is important for development and synaptic function, however, NR is absent in this synapse. Despite that, we found changes in the short-term plasticity paradigms in mutant larval NMJ. Together our results show that larval NMJ and the adult brain relies on Dlg for short-term memory/plasticity, but the mechanisms differ in the two types of synapses.

摘要

脊椎动物的Dlg-MAGUK 家族支架蛋白参与谷氨酸受体向突触后密度的募集、聚类和锚定,特别是对于长时程记忆和 LTP 所必需的 NMDA 型谷氨酸受体 (NRs)。在脊椎动物中,该亚家族的唯一基因产生两种主要产物,广泛表达的 和局限于神经系统的 。在成年大脑中,NRs 表达,参与记忆,然而,Dlg 在这些过程中的作用及其与 NRs 的关系尚未得到充分探索。在这里,我们表明 突变体在嗅觉联想学习范式中表现出短期记忆缺陷。这些缺陷依赖于 Mushroom Body (MB) 突触中 DlgS97 的存在。此外,在成年大脑中,Dlg 与 NRs 免疫共沉淀。Dlg 也在前和后突触中在幼虫的神经肌肉接头 (NMJ) 中表达,对于发育和突触功能很重要,然而,NR 在这个突触中不存在。尽管如此,我们发现 突变体幼虫 NMJ 的短期可塑性模式发生了变化。总之,我们的研究结果表明,幼虫 NMJ 和成年大脑依赖于 Dlg 进行短期记忆/可塑性,但这两种类型的突触的机制不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4366/9409279/1837b7cb0080/ijms-23-09187-g001.jpg

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