Sandbox Reserved 1649: Difference between revisions
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The binding of Zn2+ on NR2A generates an allosteric modulation of NMDA receptor, leading to its closure. The molecular mechanisms by which the NTD can communicate the inhibitory change of conformation to the rest of the receptor is still unknown. Nevertheless, the LBD was identified as a major intermediate between the NTD to the channel gate. | The binding of Zn2+ on NR2A generates an allosteric modulation of NMDA receptor, leading to its closure. The molecular mechanisms by which the NTD can communicate the inhibitory change of conformation to the rest of the receptor is still unknown. Nevertheless, the LBD was identified as a major intermediate between the NTD to the channel gate. | ||
It seems that H+ would also inhibits NR2A by conformational changes. Then, it has been proposed that zinc exerts its inhibitory action on NR1/NR2A receptors through an enhancement of tonic proton inhibition. According to this model, the presence of protons is required for zinc inhibition to occur. | It seems that H+ would also inhibits NR2A by conformational changes. Then, it has been proposed that zinc exerts its inhibitory action on NR1/NR2A receptors through an enhancement of tonic proton inhibition. According to this model, the presence of protons is required for zinc inhibition to occur. <ref name="Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition">DOI 10.1016/j.neuron.2010.08.011</ref> | ||
'''• Inhibition by CK2 indirectly on NR2A''' | '''• Inhibition by CK2 indirectly on NR2A''' | ||
[https://en.wikipedia.org/wiki/Casein_kinase_2 Casein Kinase 2] (CK2) determines the NR2 subunit content of synaptic NMDA. Indeed, CK2 phosphorylates NR2B subunit in response to activity, what regulates the number of synaptic NR2A and NR2B. Indeed, CK2 phosphorylation leads to NR2B endocytosis and remove NR2B from synapses, resulting in an increase in synaptic NR2A expression. <ref name=" | [https://en.wikipedia.org/wiki/Casein_kinase_2 Casein Kinase 2] (CK2) determines the NR2 subunit content of synaptic NMDA. Indeed, CK2 phosphorylates NR2B subunit in response to activity, what regulates the number of synaptic NR2A and NR2B. Indeed, CK2 phosphorylation leads to NR2B endocytosis and remove NR2B from synapses, resulting in an increase in synaptic NR2A expression. <ref name="Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors">DOI 110.1016/j.neuron.2010.08.011</ref> | ||
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On the contrary, the palmitoylation of the second cluster by distinct palmitoyl transferases causes receptors accumulation in the Golgi apparatus and so reduces receptor surface expression. | On the contrary, the palmitoylation of the second cluster by distinct palmitoyl transferases causes receptors accumulation in the Golgi apparatus and so reduces receptor surface expression. | ||
Since palmitoylation is reversible, by modulating phosphorylation on NR2A thanks to this dual palmitoylation, the traffiking of NMDA receptors can be regulated. Palmitoylation of Cystein cluster I regulates NMDA receptor internalization whereas palmitoylation of Cys cluster II retains the receptor in the Golgi apparatus. It is important because it controls the number of effective NMDA receptors at the surface of the cell, which has an impact on the neuronal function. <ref name=" | Since palmitoylation is reversible, by modulating phosphorylation on NR2A thanks to this dual palmitoylation, the traffiking of NMDA receptors can be regulated. Palmitoylation of Cystein cluster I regulates NMDA receptor internalization whereas palmitoylation of Cys cluster II retains the receptor in the Golgi apparatus. It is important because it controls the number of effective NMDA receptors at the surface of the cell, which has an impact on the neuronal function. <ref name="Dual Palmitoylation of NR2 Subunits Regulates NMDA Receptor Trafficking">DOI 10.1016/j.neuron.2009.08.017</ref> | ||
