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The function of GluR1 and GluR2 in cerebellar and hippocampal LTP and LTD is regulated by interplay of phosphorylation and O-GlcNAc modification

Din, Nasirud
Ahmad, Ishtiaq
Ul Haq, Ikram
Elahi, Sana
Shakoori, A. R.
Published in Journal of Cellular Biochemistry. 2010, vol. 109, no. 3, p. 585-597
Abstract 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.
Keywords Acetylglucosamine/metabolismAmino Acid SequenceCerebellum/ physiologyHippocampus/ physiologyHumansLong-Term Potentiation/ physiologyLong-Term Synaptic Depression/ physiologyMolecular Sequence DataNeuronal PlasticityPhosphorylationReceptors, AMPA/genetics/ metabolismSequence Alignment
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PMID: 20052678
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