Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan.
J Cell Biochem. 2010 Feb 15;109(3):585-97. doi: 10.1002/jcb.22436.
Long-term potentiation (LTP) and long-term depression (LTD) are the current models of synaptic plasticity and widely believed to explain how different kinds of memory are stored in different brain regions. Induction of LTP and LTD in different regions of brain undoubtedly involve trafficking of AMPA receptor to and from synapses. Hippocampal LTP involves phosphorylation of GluR1 subunit of AMPA receptor and its delivery to synapse whereas; LTD is the result of dephosphorylation and endocytosis of GluR1 containing AMPA receptor. Conversely the cerebellar LTD is maintained by the phosphorylation of GluR2 which promotes receptor endocytosis while dephosphorylation of GluR2 triggers receptor expression at the cell surface and results in LTP. The interplay of phosphorylation and O-GlcNAc modification is known as functional switch in many neuronal proteins. In this study it is hypothesized that a same phenomenon underlies as LTD and LTP switching, by predicting the potential of different Ser/Thr residues for phosphorylation, O-GlcNAc modification and their possible interplay. We suggest the involvement of O-GlcNAc modification of dephosphorylated GluR1 in maintaining the hippocampal LTD and that of dephosphorylated GluR2 in cerebral LTP.
长时程增强（LTP）和长时程抑制（LTD）是目前的突触可塑性模型，被广泛认为可以解释不同类型的记忆是如何储存在不同的大脑区域中的。不同脑区 LTP 和 LTD 的诱导无疑涉及到 AMPA 受体在突触前后的运输。海马体 LTP 涉及 AMPA 受体 GluR1 亚基的磷酸化及其向突触的传递，而 LTD 则是 GluR1 包含的 AMPA 受体去磷酸化和内吞作用的结果。相反，小脑 LTD 是通过 GluR2 的磷酸化来维持的，这种磷酸化促进了受体的内吞作用，而 GluR2 的去磷酸化则触发了受体在细胞表面的表达，从而导致 LTP。磷酸化和 O-GlcNAc 修饰的相互作用在许多神经元蛋白中被称为功能开关。在这项研究中，我们假设，通过预测不同 Ser/Thr 残基的磷酸化、O-GlcNAc 修饰及其可能的相互作用的潜力，一种相同的现象是 LTD 和 LTP 转换的基础。我们提出，去磷酸化的 GluR1 的 O-GlcNAc 修饰参与维持海马 LTD，而去磷酸化的 GluR2 的 O-GlcNAc 修饰参与维持大脑 LTP。
