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• W2894941693 abstract "Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and metabotropic glutamate receptor 5 (mGlu₅) are critical signaling molecules in synaptic plasticity and learning/memory. Here, we demonstrate that mGlu₅ is present in CaMKII<i>α</i> complexes isolated from mouse forebrain. Further in vitro characterization showed that the membrane-proximal region of the C-terminal domain (CTD) of mGlu_5a directly interacts with purified Thr286-autophosphorylated (activated) CaMKII<i>α</i>. However, the binding of CaMKII<i>α</i> to this CTD fragment is reduced by the addition of excess Ca²⁺/calmodulin or by additional CaMKII<i>α</i> autophosphorylation at non-Thr286 sites. Furthermore, in vitro binding of CaMKII<i>α</i> is dependent on a tribasic residue motif Lys-Arg-Arg (KRR) at residues 866–868 of the mGlu_5a-CTD, and mutation of this motif decreases the coimmunoprecipitation of CaMKII<i>α</i> with full-length mGlu_5a expressed in heterologous cells by about 50%. The KRR motif is required for two novel functional effects of coexpressing constitutively active CaMKII<i>α</i> with mGlu_5a in heterologous cells. First, cell-surface biotinylation studies showed that CaMKII<i>α</i> increases the surface expression of mGlu_5a. Second, using Ca²⁺ fluorimetry and single-cell Ca²⁺ imaging, we found that CaMKII<i>α</i> reduces the initial peak of mGlu_5a-mediated Ca²⁺ mobilization by about 25% while doubling the relative duration of the Ca²⁺ signal. These findings provide new insights into the physical and functional coupling of these key regulators of postsynaptic signaling." @default.
• W2894941693 created "2018-10-12" @default.
• W2894941693 creator A5001941983 @default.
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• W2894941693 date "2018-10-03" @default.
• W2894941693 modified "2023-09-26" @default.
• W2894941693 title "Activated CaMKII<i>α</i>Binds to the mGlu₅Metabotropic Glutamate Receptor and Modulates Calcium Mobilization" @default.
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• W2894941693 doi "https://doi.org/10.1124/mol.118.113142" @default.
• W2894941693 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6207916" @default.
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• W2894941693 hasPublicationYear "2018" @default.
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